MetaCyc Release Notes History

This document summarizes the release history of MetaCyc.

 

MetaCyc Statistics by Year

	2023	2022	2021	2020	2019	2018	2017	2016	2015	2014	2013	2012	2011	2010	2009	2008	2007	2006	2005	2004	2003	2002	2001	Description
Metabolic Pathways	3128	3085	2980	2847	2766	2698	2609	2507	2411	2255	2097	1928	1790	1642	1436	1203	1010	800	692	528	491	460	445	Number of metabolic pathways, excluding superpathways
Reactions	18819	18391	17509	16810	16151	15413	14654	13924	13074	12074	11409	10481	9609	8988	8248	7312	6576	5871	5520	4955	4858	4294	4218	Number of biochemical reactions
Enzymes	14320	14120	13540	12943	12564	12111	11680	11306	10789	10100	9148	8426	7611	6912	6056	5127	4582	3527	3029	1940	1618	1267	1115	Number of enzymes that catalyze biochemical reactions
Chemical Compounds	19173	18785	17656	16631	15935	15263	14411	13585	12792	11681	10965	10157	9277	8869	8363	7234	6561	5254	4817	3551	3029	2404	2335	Number of chemical compounds
Organisms	3443	3413	3325	3161	3067	2980	2914	2831	2740	2579	2460	2362	2216	2072	1834	1549	1077	729	601	302	222	174	158	The number of distinct taxa that pathways in MetaCyc are labeled to occur in [more]
Citations	76283	74193	70088	65725	62408	58954	55666	51482	47838	43818	37570	36796	31145	26848	21713	17916	15875	10658	8599	5050	3619	2718	2381	Number of distinct references cited within MetaCyc

Note: The statistics for each year pertain to the last MetaCyc version released in that year.
NA = Not available.
Click here for information on the taxonomic distribution of MetaCyc pathways.

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Release Notes for MetaCyc Version 27.1

MetaCyc KB Statistics

Pathways	3128
Reactions	18819
Enzymes	14320
Chemical Compounds	19173
Organisms	3443
Citations	76283
EC numbers	6716
Textbook Page Equivalency	11562

Released on Aug 28, 2023

New and Updated Pathways

We have added 23[more info] new pathways to MetaCyc since the last release and revised 1 existing pathway, for a total of 24 new and revised pathways.

Bacterial Biosynthetic Pathways

A new pathway describes the biosynthesis of poly-β-1,6-N-acetyl-D-glucosamine (PNAG), an exopolysaccharide that is a key component of the biofilm matrix of many pathogenic bacteria. Two new pathways describe the biosynthesis of the capsular polysaccharides of the two most important Streptococcus pneumoniae serovars. Another pathway describes the production of UDP-N-acetyl-α-D-mannosamine, a component of many bacterial and archaeal polysaccharides.

• poly-β-1,6-N-acetyl-D-glucosamine biosynthesis
• Streptococcus pneumoniae serotype 2 capsular polysaccharide biosynthesis
• Streptococcus pneumoniae serotype 4 capsular polysaccharide biosynthesis
• UDP-N-acetyl-α-D-mannosamine biosynthesis

Bacterial Degradation Pathways

A new pathway describes the activity of the recently discovered enzyme EC 4.3.1.33, (R)-1-hydroxy-2-aminoethylphosphonate ammonia-lyase, an enzyme with a narrow substrate specificity which expands the range of phosphonates known to be utilized by bacteria. Many Gram-negative bacterial species carry plasmids such as R773, which contains the arsABCD genes for arsenate detoxification (that process is described in arsenate detoxification I). Some organisms, such as E. coli MG1655, do not carry such a plasmid and rely on chromosomal genes, as described by a new pathway for arsenate detoxification. The marine bacterium Pseudoalteromonas sp. CF6-2 can kill a variety of Gram-positive bacteria by attacking their cell-wall peptidoglycan and can use the liberated D-glutamate as its sole carbon and nitrogen source as described in a new D-glutamate degradation pathway. A new pathway describes how bacteria can convert glycine to pyruvate and ammonium, satisfying the need for both carbon and nitrogen (this pathway is also a part of the photorespiration pathway found in higher plants). Another new pathway describes the degradation of the toxic compound methylglyoxal by the enzyme glyoxalase III (officially named EC 4.2.1.130, D-lactate dehydratase), which converts methylglyoxal to (R)-lactate in a single step.

• (1R)-(2-amino-1-hydroxyethyl)phosphonate degradation
• arsenic detoxification XI
• D-glutamate degradation
• glycine degradation
• L-cysteine degradation IV
• methylglyoxal degradation IX

Plant Biosynthetic Pathways

The kavalactones are known for their psychoactive effects and have pharmaceutical potentials for treating anxiety, insomnia and pain. This pathway describes the use of a cloned styrylpyrone methyltransferase from the kava plant to produce kavalactones in E. coli.

• 5,6-dehydrokavain biosynthesis (engineered)

Fungal Biosynthetic Pathways

The sphingofungins are a group of structurally related compounds produced by fungi that specifically inhibit EC 2.3.1.50, serine C-palmitoyltransferase, the enzyme that catalyzes the initial step in sphingolipid biosynthesis. This new pathway describes the biosynthesis of sphingofungins B, C, and D by the human pathogenic fungus Aspergillus fumigatus.

• sphingofungin B-D biosynthesis

Electron Transfer Pathways

We have added four new electron transfer pathways characterized from the opportunistic pathogenic bacterium Staphylococcus epidermidis.

• glycerol 3-phosphate to cytochrome aa₃ oxidase electron transfer
• NADH to cytochrome aa₃ oxidase electron transfer
• NADH to nitrate electron transfer
• succinate to cytochrome aa₃ oxidase electron transfer

Archaeal Pathways

Tetrahydromethanopterin and tetrahydrosarcinapterin are alternatives to folate used by members of the archaea. A new pathway describes the latter part of the methanogenesis process in organisms that produce tetrahydromethanopterin. Another pathway describes the production of tetrahydrosarcinapterin by the ATP-dependent glutamylation of tetrahydromethanopterin.

• methyl-coenzyme M oxidation to CO₂ II
• tetrahydrosarcinapterin biosynthesis

Mammalian Pathways

Aspartame is a low-calorie sweetener used extensively worldwide in a wide variety of foods and beverages. A new pathway describes its degradation in the mammalian intestine. Human milk oligosaccharides are abundant carbohydrates fundamental to infant health and development. They account for 11-17% of the milk. More than a hundred different oligosaccharides have been characterized from human milk; a new pathway describes the biosynthesis of the most common ones.

• aspartame degradation
• human milk oligisaccharides biosynthesis

Salvage Pathways

Eukaryotes produce NAD de novo from L-tryptophan. A new eukaryotic pathway describes the phosphorylation of the vitamin B3 compound β-D-ribosylnicotinate (nicotinate riboside), which allows its salvage for production of NAD. Another salvage pathway describes the conversion of 5-(2-hydroxyethyl)-4-methyl-1,3-thiazole-2-carboxylate, a degradation product of an intermediate in thiamine diphosphate biosynthesis, back to thiamine diphosphate.

• nicotinate riboside salvage pathway I
• thiamine diphosphate salvage V

Other Pathways

Aminoacyl-tRNA synthetases join amino acids with their cognate tRNAs in high fidelity reactions that define the genetic code. Most of these enzymes are specific for a particular amino acid. The reaction starts by activation of the amino acid to an adenylate form, which is is initially held noncovalently in the active site before being transferred to the 2' or 3' hydroxyl group of the terminal ribose of the tRNA. The fidelity required to ensure proper protein biosynthesis is estimated to be 1 in 3300. However, many of the enzymes are not specific enough during the adenylation step, resulting in activation of the wrong amino acid at a rate that is too high. To ensure proper protein synthesis, mechanisms known as "editing" exist for the release of misacylated amino acids before they are transferred to the tRNA.

• misacylated tRNA editing

Updated Pathways

The following pathways have been modified to reflect new information that has become available since they were last curated.

• diadinoxanthin and fucoxanthin biosynthesis (diatoms)

Other Improvements

Update of EC Reactions

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of August 2023) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6698 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 27.0

MetaCyc KB Statistics

Pathways	3105
Reactions	18566
Enzymes	14250
Chemical Compounds	18973
Organisms	3430
Citations	75205
EC numbers	6698
Textbook Page Equivalency	11427

Released on Apr 12, 2023

New and Updated Pathways

We have added 24_{[more info]} new pathways to MetaCyc since the last release and revised 2 existing pathways, for a total of 26 new and revised pathways.

Bacterial Biosynthetic Pathways

Osmoprotectants or compatible solutes are small organic molecules with neutral charge and low toxicity that act as osmolytes and help organisms survive extreme osmotic stress. We added two new pathways for the biosynthesis of the osmoprotectants 1-(sn-glycero-3-phospho)-1D-myo-inositol, 2-O-(β-D-mannosyl-(1→2)-β-D-mannosyl)-bis(myo-inositol) 1,3'-phosphate, and 1-(sn-glycero-1-phospho)-1D-myo-inosito (see also below under archaeal pathways).

Opines are a family of low molecular weight compounds resulting from the reduction of the imine formed by condensation of an amino acid with a keto acid or a sugar. While opines are found in marine invertebrates, fungi, higher plants and mammals, they are most commonly found in plant crown gall tumors or hairy root tumors, where they are produced by bacteria of the genera Agrobacterium and Rhizobium, respectively. Each strain of Agrobacterium and Rhizobium induces and catabolizes a specific set of opines, determined by the specific Ti or Ri plasmid they possess. We have added pathways describing the biosynthesis of several opines, including D-nopaline, ornaline, mannopine, agropine, D-octopine, D-lysopine, and sulfonopine.

Two new pathways involve polyketide synthases (PKSs). The first one describes the biosynthesis of corallopyronin A - an antibiotic produced by strains of Corallococcus coralloides, a gliding and fruiting body-forming myxobacterium. It acts as a noncompetitive inhibitor of the bacterial EC 2.7.7.6, DNA-directed RNA polymerase, by binding to the RpoB switch region, interfering with RNA synthesis. Corallopyronin A is active against many Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, but is most promising against infections in which intracellular bacteria are involved. Its biosynthetic pathway involves three PKSs as well as a hybrid NRPS/PKS. The second one describes the biosynthesis of furaquinocins - a family of polyketide-isoprenoid hybrid compounds produced by Streptomyces sp. KO-3988 and related species that show a wide range of biological effects including in vitro cytotoxicity against HeLa S3 and B16 melanoma cells, antihypertensive activity, and inhibition of platelet aggregation and coagulation.

Poly-γ-glutamate (PGA) is a natural polymer that is synthesized by several bacteria (all Gram-positive), archaea, and (so far) one eukaryote. PGA has many industrial uses in wastewater treatment, medicine, the food industry, cosmetics, agriculture, and more. We added a pathway describing the biosynthesis of a PGA capsule by the pathogen Bacillus anthracis.

• 1-(sn-glycero-3-phospho)-1D-myo-inositol biosynthesis
• 2-O-(β-D-mannosyl-(1→2)-β-D-mannosyl)-bis(myo-inositol) 1,3'-phosphate biosynthesis
• 2-oxoglutarate-derived opine biosynthesis
• corallopyronin A biosynthesis
• furaquinocin biosynthesis
• mannopine and agropine biosynthesis
• poly-γ-D-glutamate biosynthesis
• pyruvate-derived opine biosynthesis I (bacteria)

Plant Biosynthetic Pathways

The cucurbitacins are a class of bitter-tasting oxygenated tetracyclic triterpenes produced by members of the Cucurbitaceae and some other plants as a means of defense against herbivores. They are based on the cucurbitane skeleton and often occur as glycosides. Many cucurbitacins induce a cytotoxic activity that inhibits cancer cell proliferation, actin polymerization, capillary permeability, and anti-inflammatory activity. Xanthones are yellow pigments restricted in occurrence to only a few families of higher plants and some fungi and lichens. Hyperxanthone E is a prenylated xanthone phytoalexin produced by Hypericum calycinum.

• cucurbitacin biosynthesis
• hyperxanthone E biosynthesis

Fungal Biosynthetic Pathways

The fungus Tolypocladium inflatum produces the cyclosporins, a group of neutral cyclic oligopeptides composed of 11 amino acids. While the native function of the compounds is to act as antifungals against competing fungi, they were found to have multiple biological effects. Cyclosporin A, the main metabolite, is a potent, specific immunosuppressant that revolutionized the field of transplantation. It is the active agent in common immunosuppressant drugs such as Sandimmune® and Neoral®. One of the 11 amino acids that compose the cyclosporines is the non-proteinogenic acid (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine (2-Bmt), the presence of which is essential for high immunosuppressive activity.

• (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine biosynthesis
• cyclosporin A biosynthesis

Bacterial Degradation Pathways

Mimosine is a non-proteinogenic amino acid, produced by the legume species Mimosa pudica and Leucaena leucocephala, that has multiple toxic effects on mammals. Ruminants from Australia and India are sensitive to it, but ruminants in Hawaii and Indonesia can consume mimosine-rich diets without showing any ill effects due to rapid bacterial degradation. We added a pathway describing the degradation of mimosine, as well as a pathway for the degradation of a related compound, 4-hydroxypyridine, which is degraded by a different set of enzymes. Carminic acid is a C-glycoside natural red pigment found in some scale insects including the American cochineals, which live as parasites exclusively on cacti belonging to the Opuntia genus. Carminic acid has been used as colorant by the Mayans, Incas, and Aztecs. During the Spanish colonial era, the dried insect powder was exported to Europe, where it became an important commodity. Today carminic acid is widely used as a colorant in the food, textile, cosmetic, paint, and coating industry. We added a pathway describing its biosynthesis (see below) as well as a pathway for its degradation by Microbacterium 5-2b. Another new pathway describes the degradation of puerarin, an isoflavone C-glucoside found in the roots of Pueraria montana lobata (kudzu vine), by the human intestinal bacterium PUE. Puerarin is the main ingredient of Kakkon-to, a famous Kampo medicine (traditional medicine in China and Japan) used for the treatment of colds. Two new pathways describe the degadation of two types of glycans: the mammalian high-mannose N-glycan, and the yeast mannan. Other bacterial degradative pathways were added for the amino acid D-alanine and the sugar L-fucose.

• 4-hydroxypyridine degradation
• carminate degradation
• D-alanine degradation
• L-fucose degradation II
• L-mimosine degradation
• mammalian high-mannose N-glycan degradation
• puerarin degradation
• yeast mannan degradation

Archaeal Pathways

A new archaeal pathway describes the biosynthesis of the osmoprotectant 1-(sn-glycero-1-phospho)-1D-myo-inositol, which is typically found in hyperthermophiles such as Archaeoglobus fulgidus. Another new pathway describes the non-carboxylating pentose bisphosphate pathway - a unique pathway found in some halobacteria for the degradation of nucleosides and nucleotides.

• 1-(sn-glycero-1-phospho)-1D-myo-inositol biosynthesis
• nucleoside and nucleotide degradation (halobacteria)

Mammalian Pathways

Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. The key protein responsible for blood clotting is fibrin - a fibrous, non-globular protein that polymerizes to form (together with platelets) a hemostatic plug over a wound site. Firbrin is produced in a non-active form called fibrinogen and must be converted into the active fibrin form by cleavage, which is catalyzed by thrombin at a wound site. There are two regulatory cascades that control the activation of fibrinogen to fibrin. We have added the primary pathway, which used to be known as the extrinsic pathway but is now referred to as the tissue factor pathway.

• blood coagulation - tissue factor pathway

Other Eukaryotic Pathways

As discussed above, carminic acid is a natural red pigment found in some scale insects including the American cochineals. As of today, only a single enzyme has been characterized from its biosynthetic pathway. However, chemical analyses have identified intermediates, leading to a proposed pathway. Intriguingly, the pathway predicts the participation of a polyketide synthase (PKS), though no genes encoding PKS have been identified in the cochineal genome. Still, an engineered pathway utilizing a plant PKS expressed in yeast or bacteria produced carminic acid as predicted.

• carminate biosynthesis

Updated Pathways

The following pathways have been modified to reflect new information that has become available since they were last curated.

• salicortin biosynthesis
• t-anethole biosynthesis

Other Improvements

Update of EC Reactions

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of October 2022) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6658 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 26.5

MetaCyc KB Statistics

Pathways	3085
Reactions	18391
Enzymes	14120
Chemical Compounds	18785
Organisms	3413
Citations	74193
EC numbers	6658
Textbook Page Equivalency	10392

Released on December 13, 2022

New and Updated Pathways

We have added 22_{[more info]} new pathways to MetaCyc since the last release. We also added one superpathway, for a total of 23 new pathways.

Bacterial Lipopolysaccharide Biosynthetic Pathways

Lipopolysaccharides (LPS) are complex compounds that can be conceptually divided into three parts: lipid A, which anchors LPS into the membrane; the core oligosaccharide, which contributes to membrane stability; and the O-antigen, which is a polysaccharide that extends away from the cell surface. Each part is a complex large molecule on its own. In order to facilitate the representation of their biosyntetic pathways, these complex pathways have been broken into a series of shorter pathways focusing on one aspect of the process, such as lipid A biosynthesis, core oligosaccharide biosynthesis, and O-antigen biosynthesis. For this release we added several pathways describing the last step in the process - the attachment of the O-antigen to the lipid A-core oligosaccharide complex.

• Brucella abortus lipopolysaccharide biosynthesis (final steps)
• Helicobacter pylori 26695 lipopolysaccharide biosynthesis (final steps)
• Porphyromonas gingivalis lipopolysaccharide (O-LPS) biosynthesis (final steps)
• Salmonella typhimurium LT2 lipopolysaccharide biosynthesis (final steps)

Biosynthesis of Polyketide Extender Units

Polyketides are secondary metabolites produced by some bacteria, fungi, plants, and animals. They are usually biosynthesized by polyketide synthase enzymes (PKS) through the decarboxylative condensation of extender units that are derived from malonyl-CoA, in a process similar to fatty acid synthesis. The biosynthesis of some polyketides involves unusual extender units, which are produced by their own specialized pathways. We added new pathways that describe the biosynthesis of three unusual extender units.

• (2R)-methoxymalonyl-[acp] biosynthesis
• (2S)-ethylmalonyl-CoA biosynthesis
• 2-allylmalonyl-CoA biosynthesis

Fungal Biosynthetic Pathways

We added four new pathways that describe the biosynthesis of fungal products. Ascomycin is a macrocyclic polyketide produced by Streptomyces hygroscopicus subsp. ascomyceticus that acts as a potent immunosuppressant that prevents T-cell proliferation. The cyathins are a family of compounds produced by fungi belonging to the genus Cyathus (bird's nest fungi), many of which show interesting biological activities. Like the cyathins, the erinacines are based on a cyathane skeleton, but they are modified with a xylose sugar. Many of the erinacines also demonstrate unique biological activities, such as potent stimulating activity for nerve-growth-factor synthesis and agonistic activity towards the kappa opioid receptor. Fumigillin is a meroterpenoid compound produced by the mold Aspergillus fumigatus that has been studied for its anti-angiogenic properties. It also has pharmaceutical potential for the treatment of microsporidiosis, and is the only effective chemical treatment currently available for honey bee nosemiasis, which is caused by parasitic fungi from the Microsporidia phylum.

• ascomycin biosynthesis
• cyathin biosynthesis
• erinacine biosynthesis
• fumagillin biosynthesis

Bacterial Degradation Pathways

N-(1-deoxy-D-fructos-1-yl)-L-asparagine (F-Asn) is an Amadori product - a type of compound that is formed spontaneously by the interaction of a reducing sugar (such as glucose or fructose) with a biological amine such as an amino acid, followed by a rearrangement to form a stable ketoamine. F-Asn occurs naturally in substantial quantities in foods, particularly after heating. We added a pathway describing its degradation by bacterial species such as Salmonella enterica, which uses F-Asn as its primary nutrient in the inflamed intestine. Another new pathway describes a cysteine salvage pathway acting on benzylated cysteine. L-canavanine is a plant product that serves as an antimetabolite of L-arginine and is involved in plant defense. Despite its toxicity it serves as a signaling molecule for free-living symbiotic bacteria to onset their symbiosis with the legume plant, and as a nutrient for bacteria living in the rhizosphere.

• N-(1-deoxy-D-fructos-1-yl)-L-asparagine degradation
• S-benzyl-L-cysteine degradation
• L-canavanine degradation II

Other Bacterial Biosynthetic Pathways

The pentitol sugar ribitol is a common component of teichoic acids and capsular polysaccharides of Gram-positive bacteria. The compound is transferred to the growing polymers from its activated form, CDP-ribitol.

• CDP-ribitol biosynthesis

Archaeal Pathways

Glycerol dialkyl glycerol tetraether lipids (GDGTs) are a class of membrane lipids synthesized by many archaea (and some bacteria). They are formed by the joining together of two archaeol-type phospholipids, and because they have two hydrophilic head groups, they form a lipid monolayer in the cell membrane instead of a bilayer, making GDGT-producing organisms exceptional among all clades of life. Macrocyclic archaeol phospholipids are generated by the same enzyme that forms GDGTs. However, in this case rather than connecting two archaeol molecules to each other, the enzyme ligates the ends of the two phytanyl chains to each other, cyclyzing the archaeol molecule.

• glycerol dibiphytanyl glycerol tetraether lipid biosynthesis
• macrocyclic archaeol phospholipid biosynthesis

Mammalian Pathways

All mammals appear to operate a glycolysis pathway from fructose at some capacity, but the pathway plays a key role in the metabolism of the naked mole-rat under low oxygen conditions. These animals tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose, which is actively accumulated and metabolized to lactate in the brain via a glycolysis pathway.

• glycolysis VI (from fructose)

Icosanoids Biosynthesis

Polyunsaturated fatty acids (PUFAs) can be oxygenated either enzymatically or in free radical-mediated reactions into hundreds of oxygenated species, many of which are mediators of cellular processes. The best-studied classes of these oxygenated mediators are the icosanoids (sometimes spelled eicosanoids). Even though the name is derived from the ancient Greek word eikosi, which means twenty, to signify the 20 carbons present in arachidonate-derives compounds, it is often used for metabolites of 18- and 22-carbon PUFAs. We added several pathways that integrate reactions that form the PUFAs by releasing them from lipids and steroids and reactions that show the most common transformations of those PUFAs into icosanoids.

• representative whole plasma arachidonate-derived icosanoids I
• representative whole plasma arachidonate-derived icosanoids II
• representative whole plasma DHA-derived icosanoids
• representative whole plasma EPA-derived icosanoids

Superpathways

Cardiolipin is one of the three most common glycerophospholipids found in bacteria. Although MetaCyc already contained several pathways describing cardiolipin biosynthesis, we have added a new superpathway that integrates several of these pathways, as well as pathways forming precursors used in cardiolipin biosynthesis.

• superpathway of cardiolipin biosynthesis (bacteria)

Other Improvements

Update of EC Reactions

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of October 2022) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6658 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 26.1

MetaCyc KB Statistics

Pathways	3063
Reactions	18285
Enzymes	14028
Chemical Compounds	18622
Organisms	3396
Citations	72987
EC numbers	6662
Textbook Page Equivalency	10308

Released on Aug 24, 2022

New and Updated Pathways

We have added 56_{[more info]} new pathways to MetaCyc since the last release and revised 16 pathways by modifying pathway diagrams, adding commentary, or updating enzyme and gene information. We also added one superpathway, for a total of 73 new and updated pathways.

Bacterial Degradation Pathways

Dicarboxylic acids such as adipate are not common in nature, but are important in the chemical manufacturing industry, mostly for the production of nylon. We added pathways for both the biosynthesis and degradation of adipate. Benzene is among the most prevalent organic contaminants in groundwater and is a major concern due to its toxicity. We added three additional variants of benzene degradation, two of which occur under anaerobic conditions. We expanded significantly our coverage of sulfoquinovose degradation with 3 new pathway variants and also added a pathway for the degradation of sulfoquinovosyl diacylglycerides and sulfoquinovosyl gl. Other new pathway variants describe the degradation of the pentitols D-arabinitol, ribitol, and xylitol, and of the uronic acids D-galacturonate and D-glucuronate. A new pathway shows how some Desulfovibrionales species can grow in the absence of sulfate on lactate as sole energy source when in syntrophic association with H₂-consuming mnogenic archaea, which keep the H₂ partial pressure low and drive the pathway forward. Finally, two different but related variants of vitamin B6 degradation have been described back in the 1950s, but only one of those was curated in MetaCyc. We now added the second variant.

• adipate degradation
• benzene degradation II (aerobic)
• benzene degradation III (anaerobic)
• benzene degradation IV (anaerobic)
• D-arabinitol degradation II
• D-galacturonate degradation III
• D-glucuronate degradation III
• lactate fermentation to acetate, CO₂ and hydrogen (Desulfovibrionales)
• ribitol degradation II
• sulfoquinovose degradation IV
• sulfoquinovose degradation V
• sulfoquinovose degradation VI
• sulfoquinovosyl diacylglycerides and sulfoquinovosyl glycerol degradation
• vitamin B₆ degradation II
• xylitol degradation II

Prokaryotic Biosynthetic Pathways

Antibiotic and toxin biosynthesis: We added 12 new pathways that describe the biosynthesis of antibiotic or toxic compounds. Antimycins are a family of related compounds that exhibit significant bioactivities, including antifungal, insecticidal, and nematocidal properties. They inhibit the mitochondrial electron transport chain by binding to EC 7.1.1.8, quinol—cytochrome-c reductase and are synthesized via a hybrid non-ribosomal peptide synthase/polyketide synthase (NRPS/PKS)-based pathway that uses the unusual starter unit 3-formamidolsalicylate. Clorobiocin, which contains a 7-hydroxy-2-aminocoumarin core, targets the bacterial DNA gyrase. Diazepinomicin is produced by some Actinobacteria. It inhibits EC 1.13.11.34, arachidonate 5-lipoxygenase, and shows cytotoxicity against a number of murine and human tumor cell lines. It is currently in phase II clinical trials for treatment of Phelan-McDermid syndrome and co-morbid epilepsy. Hygromycin B is an aminocyclitol antibiotic produced by Streptomyces hygroscopicus. It is unusual in that it is active against both prokaryotic and eukaryotic cells, using different mechanisms -- it obstructs protein synthesis by targeting 30S ribosomal subunits in bacteria and the elongation of nascent chains during the translation of polysomes in eukaryotic cells. It is produced on an industrial scale and used to treat parasite infection in poultry and livestock. Microcins are a class of gene-encoded low-molecular-mass antibacterial peptides secreted by bacteria. Microcin C is a heptapeptide with an N-formylated methionine and a C-terminal phosphoramidate linkage to adenosine, modified with an aminopropyl moiety. Following importation by target cells it is cleaved by non-specific peptidases, releasing a toxic product that targets EC 6.1.1.12, aspartate—tRNA ligase, inhibiting protein synthesis. Septacidin, produced by Streptomyces fimbriatus, was discovered in 1963 and has antitumor and antifungal activities. Several derivatives were shown to act as differentiation inducers of leukemia cells. Sibiromycin, produced by actinomycetes, belongs to the pyrrolobenzodiazepines. It binds to the minor groove of a double-stranded DNA with picomolar affinity, leading to DNA strand breakage, inhibition of DNA processing enzymes or transcription factors, and modulation of signalling pathways. Despite its potency against cancer cells sibiromycin is not a suitable drug due to its cardiotoxic properties. However, modified versions are promising anticancer drug candidates. Sulfazecin is a monobactam antibiotic discovered in the early 1980s in Paraburkholderia acidicola. Like many other monobactam antibiotics it is resistant to β-lactamases and is thus a promising lead compound for the development of β-lactamase-resistant antibiotics.

Cyanobacteria produce a large number of bioactive compounds. Apratoxin A, produced by the cyanobacterium Moorena bouillonii, is a complex molecule with potent cytotoxicity to cancer cells. The curacins, which are produced by marine cyanobacteria via a mixed NRPS/PKS pathway, have unusual structural features, containing a cyclopropane group, a thiazoline moiety, and a terminal double bond. Curacin A is a potent antiproliferative agent that inhibits the binding of colchicine to tubulin and arrests mitosis. Hectochlorin is a lipopeptide originally isolated from the filamentous cyanobacterium Moorena producens. It exhibits potent antifungal activity against the yeast Candida albicans and a number of plants pathogens, as well as inhibiting growth of human cell lines by hyperpolymerization of actin.

• antimycin biosynthesis
• apratoxin A biosynthesis
• clorobiocin biosynthesis
• curacin A biosynthesis
• diazepinomicin biosynthesis
• dTDP-sibirosamine biosynthesis
• hectochlorin biosynthesis
• hygromycin B biosynthesis
• microcin C biosynthesis
• septacidin biosynthesis
• sibiromycin biosynthesis
• sulfazecin biosynthesis
• superpathway of novobiocin biosynthesis

Cell components biosynthesis. During this period we introduced several pathways that describe the biosynthesis of lipopolysaccharides by El Tor strains of Vibrio cholerae, which are the strains responsible for the current cholera epidemic.

• Kdo transfer to lipid IV_A (Vibrio cholerae serogroup O1 El Tor)
• Kdo-lipid A biosynthesis (Vibrio cholerae serogroup O1 El Tor)
• lipid A modification (glycine addition, Vibrio cholerae)
• lipid IV_A biosynthesis (Vibrio cholerae serogroup O1 El Tor)

Other microbial biosynthetic pathways. Other bacterial biosynthetic pathways include synthesis of 3-thia-L-glutamate by Pseudomonas syringae. Although the role of this compound is still not known, its synthesis is an example of an unusual type of pathway in which a ribosomally synthesized and post-translationally modified peptide (RiPP) is used as a scaffold. 7,8-Dimethylmenaquinone is a menaquinone derivative of uncertain function that is restricted to species of the class Coriobacteriia (phylum Actinobacteria). We also added a pathway for the biosynthesis of erythritol by the the wine lactic acid bacterium Oenococcus oeni. Erythritol is used as a natural sweetener and is produced on an industrial scale. The myxochelins are hydroxamate-type iron chelators produced by Myxobacteria. Two new archaeal pathways describe the production of C25,25 CDP-archaeol by the aerobic thermophilic archaeon Aeropyrum pernix, and a variant of NAD biosynthesis that utilizes EC 1.4.1.21, aspartate dehydrogenase, enabling NAD biosynthesis under anaerobic conditions (this latter pathway is also found in some thermophilic bacterial species).

• 3-thia-L-glutamate biosynthesis
• 7,8-dimethylmenaquinone biosynthesis
• adipate biosynthesis
• C_25,25 CDP-archaeol biosynthesis
• erythritol biosynthesis I
• myxochelin A and B biosynthesis
• NAD de novo biosynthesis III

Eukaryotic Biosynthetic Pathways

Aspoquinolone and penigequinolone are quinilone alkaloids produced by fungi from the Aspergillus and Penicillium genera that have insecticidal activities. Leporin B is a fungal N-methoxy pyridone alkaloid that has cytotoxicity against human tumor cell lines as well as antibacterial activity. Mannosylerythritol lipids are amphiphilic glycolipids that display high surface activity and act as biodetergents (biosurfactants). They are produced by yeast strains that belong to the Ustilago and Moesziomyces genera and are of growing biotechnological interest as a sustainable alternative for chemical surfactants. A new pathway describes the synthesis of taurine in reptilian eggs during embryo development. We also added the eukaryotic variant of erythritol biosynthesis, which is used on an industrial scale through the fermentation of sugars by some yeasts, such as Moniliella sp., and the mammalian variant of lipoate biosynthesis.

• aspoquinolone biosynthesis
• erythritol biosynthesis II
• leporin B biosynthesis
• lipoate biosynthesis and incorporation V (mammals)
• mannosylerythritol lipids biosynthesis
• penigequinolone biosynthesis
• taurine biosynthesis III

Icosanoids Biosynthesis

Polyunsaturated fatty acids (PUFAs) can be oxygenated either enzymatically or in free radical-mediated reactions into hundreds of oxygenated species including regio- and stereo-isomers of mono- and poly-hydroxy-, hydroperoxy-, epoxy- and oxo-fatty acids, prostanoids, isoprostanes, and leukotrienes, which act as mediators of cellular processes. The best-studied classes of these oxygenated mediators are the icosanoids (sometimes spelled eicosanoids), whose name is derived from the ancient Greek word eikosi, which means twenty, to signify the 20 carbons in these compounds (though the term is often used to include metabolites of 18- and 22-carbon PUFAs). We added several pathways that describe the transformations of the PUFAs linoleate, α-linolenate, di-homo-γ-linolenate, icosapentaenoate, arachodonate, and docosahexaenoate to their derivatives. Several types of icosanoids, namely the lipoxins, resolvins, protectins, and maresins, as well as their sulfido-conjugates, which are known collectively as "specialized pro-resolving mediators" (SPMs), play a key role in the pro-resolution phase of inflammation. We added new pathways describing the biosynthesis of maresins, protectins, and peptido-conjugates in tissue regeneration.

• α-linolenate metabolites biosynthesis
• arachidonate metabolites biosynthesis
• di-homo-γ-linolenate metabolites biosynthesis
• linoleate metabolites biosynthesis
• docosahexaenoate metabolites biosynthesis
• icosapentaenoate metabolites biosynthesis
• maresin biosynthesis
• peptido-conjugates in tissue regeneration biosynthesis
• protectin biosynthesis

Photorespiration Pathways

EC 4.1.1.39, ribulose-bisphosphate carboxylase, commonly referred to as ribulose bisphosphate carboxylase/oxygenase or RubisCO, is a bifunctional enzyme that catalyzes both the carboxylation and oxygenation of D-ribulose-1,5-bisphosphate (RuBP). Under conditions of low CO₂ and high O₂ concentrations, RuBP is oxidized to 3-phospho-D-glycerate and 2-phosphoglycolate. The latter cannot be used in the Calvin-Benson-Bassham cycle and, instead, is salvaged via the photorespiration pathway. While the pathway is similar in all organisms that possess it, some differences exist among the variants that operate in green plants, cyanobacteria, and green algae. We have modified our existing pathway and added two new variants to capture these differences.

• photorespiration II
• photorespiration III

Updated Pathways

The following pathways have been modified to reflect new information that has become available since they were last curated.

• acylceramide biosynthesis and processing
• adipate degradation
• di-myo-inositol phosphate biosynthesis
• dissimilatory sulfate reduction I (to hydrogen sufide))
• fatty acid biosynthesis initiation (mitochondria)
• inositol diphosphates biosynthesis
• L-phenylalanine degradation II (anaerobic)
• phosphatidylglycerol biosynthesis I
• phosphatidylglycerol biosynthesis II
• photorespiration I
• quinolinone B biosynthesis
• spinosyn biosynthesis
• sulfite oxidation II
• taurine biosynthesis I
• taurine biosynthesis II
• viridicatin biosynthesis

Other Improvements

Update of EC Reactions

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of July 2022) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6662 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 26.0

MetaCyc KB Statistics

Pathways	3006
Reactions	17780
Enzymes	13698
Chemical Compounds	18124
Organisms	3349
Citations	71322
EC numbers	6621
Textbook Page Equivalency	10944

Released on April 13, 2022

New and Updated Pathways

We have added 26_{[more info]} new pathways to MetaCyc since the last release and revised 38 pathways by modifying pathway diagrams, adding commentary, or updating enzyme and gene information. We also updated one superpathway, for a total of 65 new and updated pathways.

Pentose sugar degradation

Pentose sugars, including D-xylose, L-arabinose, and D-arabinose, are metabolized through three main types of pathways. The first type, common in bacteria, uses isomerases, kinases, and epimerases to yield xylulose 5-phosphate, which feeds into the pentose phosphate pathway. In the second type of pathway, which involves reductases and dehydrogenases and is found mainly in yeast and fungi, pentoses are converted into a sugar alcohol, which is then converted to ribulose 5-phosphate or xylulose 5-phosphate, again feeding into the pentose phosphate pathway. The third type is partially analogous to the archaeal non-phosphorylative Entner-Doudoroff pathway variant, and has been sub-classified into three routes. All routes share the early steps, in which the pentoses are converted into 2-dehydro-3-deoxypentonate (KDP) through the participation of aldose 1-dehydrogenases, lactonases, and acid-sugar dehydratases. The next steps are route-dependent: in the first route (the Dahms pathway) the KDP intermediate is cleaved through an aldolase reaction to pyruvate and glycoaldehyde. In the second route (the Weimberg pathway) the KDP intermediate is converted into 2-oxoglutarate. In the third route the KDP intermediate is oxidized into 5-hydroxy-2,4-dioxopentanoate, which is then hydrolyzed into glycolate and pyruvate. We have expanded our coverage to include all possible pathways and revised our summaries to provide a more comprehensive background.

• D-arabinose degradation I
• D-arabinose degradation II
• D-arabinose degradation III
• D-arabinose degradation IV
• D-arabinose degradation V
• D-xylose degradation I
• D-xylose degradation III
• D-xylose degradation IV
• D-xylose degradation V
• D-xylose degradation VI
• L-arabinose degradation I
• L-arabinose degradation II
• L-arabinose degradation III
• L-arabinose degradation IV
• L-arabinose degradation V

Glucosinolate biosynthesis

The glucosinolates are secondary metabolites found in 16 plant families, including agriculturally important crop plants of the Brassicaceae such as cabbage, mustard, oilseed rape, and broccoli, as well as the model plant Arabidopsis thaliana, and are responsible for the typical sharp taste and odor of these plants. The glucosinolates are substituted β-thioglucosidic N-hydroxysulfates that are formed from any one of eight amino acids and are grouped into aliphatic, aromatic, and indolic types. Glucosinolates are stored in the vacuole and come into contact with the enzyme myrosinase (EC 3.2.1.147) upon breakage of the cell. Myrosinase de-glucosylates the glucosinolates, resulting in formation of nitriles, isothiocyanates, or thiocyanates. The configuration of the double bond in the glucosinolate structure has been controversial - some publications report it to be (Z) while others claim it is (E). As a result, the structures in MetaCyc have been inconsistent. We have recently confirmed with experts in the field that all glucosinolates have a (Z) configuration, and have updated all structures and pathways accordingly.

• glucosinolate activation
• aromatic glucosinolate activation
• indole glucosinolate activation (intact plant cell)
• glucosinolate biosynthesis from dihomomethionine
• glucosinolate biosynthesis from hexahomomethionine
• glucosinolate biosynthesis from homomethionine
• glucosinolate biosynthesis from pentahomomethionine
• glucosinolate biosynthesis from phenylalanine
• glucosinolate biosynthesis from tetrahomomethionine
• glucosinolate biosynthesis from trihomomethionine
• glucosinolate biosynthesis from tryptophan
• glucosinolate biosynthesis from tyrosine

Biosynthesis of compounds of pharmacological importance

We have curated several pathways for the biosynthesis of secondary metabolites of pharmacological importance. The ansamitocins are a family of 19-membered macrocyclic lactam antibiotics that are synthesized by some plant and bacterial species. Some members of this family, such as maytansine, possess extremely potent cytotoxicity against various tumor cells. A derivative of maytansine, named mertansine, is used in several antibody-drug conjugates against metastatic breast cancer. The depside compound atranorin is one of the most common lichen secondary metabolites and has antibacterial activity against both Gram-positive and Gram-negative bacteria, antifungal activity, antiprotozoal activity, antioxidant activity, photoprotective activity, and cytotoxic and antiproliferative activities. The depsidone grayanic acid, another lichen product, has been proposed to provide allelopathic defense and light screening to the organisms. Isoorientin is a C-glycoside flavone that has been identified in a number of plants that possesses strong antioxidant, anti-inflammatory, antidiabetic and anti-obesity properties. Leinamycin is an antitumor antibiotic produced by Streptomyces atroolivaceus that features an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. Malbrancheamide is a complex halogenated indole alkaloid produced by some fungi that has significant vasorelaxant effects. The tropane alkaloids are secondary metabolites with very complex structures that are found mostly in plants that belong to the Solanaceae family. They include the medicinal alkaloids (S)-atropine and scopolamine, which act on mammalian nervous systems. Finally, valinomycin is a cyclooligomer depsipeptide produced by several Streptomyces strains that has diverse biological activities including antifungal, antibacterial, insecticidal-nematocidal, antiparasitic, antiviral , and antitumor activities.

• ansamitocin P biosynthesis
• atranorin biosynthesis
• grayanate biosynthesis
• isoorientin biosynthesis II
• leinamycin biosynthesis
• malbrancheamide biosynthesis
• tropane alkaloids biosynthesis
• valinomycin biosynthesis

Other biosynthetic pathways

(3R)-N-[(2S)-1-hydroxy-6-[(3R)-3-isocyanobutanamido]hexan-2-yl]-3-isocyanobutanamide is an isonitrile lipopeptide that is produced by many actinobacerial species. Although its role is not understood, it was reported to be a virulence factor of Mycobacterium tuberculosis. Its biosynthetic pathway provides a new, unprecendented way of producing isonitrile groups. Brassinosteroids are steroidal phytohormones that regulate various important physiological and developmental processes, such as cell elongation and division, pollen fertility, photomorphogenesis, differentiation of vascular elements, and stress resistance. Brassinolide is the most biologically active brassinosteroid. We have extensively updated a brassinolide biosynthetic pathway known as the C-22 oxidation branch. Calystegines are nortropane alkaloids found in some Solanaceae species. They are related to tropane alkaloids, but have no medicinal use. The mycobactins are 2-hydroxyphenyloxazoline-containing siderophores that are essential for the survival of pathogenic Mycobacterium species in their hosts. A new pathway describes the complex biosynthesis of NiFe(CO)(CN)₂, the cofactor of [NiFe] hydrogenases. N¹-methyl-N³-aminocarboxypropyl-pseudouridine (m¹acp³ψ) is considered the most complex modification found in eukaryotic rRNA. The modified base is located at the tip of helix 31 of the 18S rRNA , and is strongly conserved in eukaryotes as well as in archaea. Plasmalogens are a type of a glycerophospholipid characterized by the presence of a vinyl ether linkage at the sn-1 position and an ester linkage at the sn-2 position. They are found in animals and some anaerobic bacteria, but not in plants, fungi, or most aerobic bacteria, except myxobacteria. We have added the pathway that occurs in anaerobic bacteria. Other new biosynthetic pathways describe CoA biosynthesis in archaea, and the major route of salicylate biosynthesis in plants.

• (3R)-N-[(2S)-1-hydroxy-6-[(3R)-3-isocyanobutanamido]hexan-2-yl]-3-isocyanobutanamide biosynthesis
• brassinolide biosynthesis II
• calystegine biosynthesis
• coenzyme A biosynthesis III (archaea)
• mycobactin biosynthesis
• N¹-methyl-N³-aminocarboxypropyl-pseudouridine-modified rRNA biosynthesis
• NiFe(CO)(CN)₂ cofactor biosynthesis
• plasmalogen biosynthesis II (anaerobic)
• salicylate biosynthesis II

Degradation Pathways

D-tagatose is the C-4 epimer of D-fructose. It is a low-calorie natural sugar present in small amounts in fruits and milk products, and can replace sucrose in food. Its low glycemic index and antihyperglycemic effect make D-tagatose a promising sweetener. We added a pathway for its degradation. L-carnitine is a zwitterionic quaternary amine carboxylate that has essential and diverse roles in intermediary metabolism in all living kingdoms, and γ-butyrobetaine is a metabolite involved in the biosynthesis and degradation of L-carnitine. We updated two of the L-carnitine degradation pathways, and expanded our coverage of γ-butyrobetaine degradation from one to three pathways. Glycine betaine is a very efficient osmolyte found in a wide range of bacteria and plants, where it accumulates at high cytoplasmic concentrations in response to osmotic stress to act as an osmoprotectant. We have added a new glycine betaine degradation pathway and revised an existing one. We have also updated pathways for syringate and toluene degradation to reflect new knowledge.

• D-tagatose degradation
• γ-butyrobetaine degradation I
• γ-butyrobetaine degradation II
• γ-butyrobetaine degradation III
• glycine betaine degradation I
• glycine betaine degradation III
• L-carnitine degradation I
• L-carnitine degradation III
• syringate degradation
• toluene degradation to benzoyl-CoA (anaerobic)

Protein glycosylation in yeast

Protein O-mannosylation is an essential protein modification in fungi and animals. In the yeast Saccharomyces cerevisiae mannosyl O-glycans are short oligomannose chains that are attached via a glycosidic bond in α anomeric configuration to the hydroxyl group of Ser or Thr residues. We updated the pathway describing this modification. N-linked glycosylation is an important protein modification in which oligosaccharides are attached to an Asn residue. This type of glycosylation is found in eukaryotes and archaea, and very rarely in bacteria. The pathway leading to the biosynthesis of a tetradecasaccharide precursor is highly conserved, but later processing and elongation steps differ among different organisms. We have added two new pathways that describe late stages of N-glycosylation in yeast. One pathway applies to proteins targeted for retention in cellular organelles, while the other applies to proteins that are destined to the cell wall and to some periplasmic proteins.

• protein N-glycosylation processing of mannoproteins (cis-Golgi, yeast)
• protein N-glycosylation processing of proteins targeted for retention in cellular organelles (cis-Golgi, yeast)
• protein O-mannosylation I (yeast)

Assorted other pathways

EC 6.2.1.1, acetate佑oA ligase, usually converts acetate to acetyl-CoA at the expense of ATP. However, in the bacterium Syntrophus aciditrophicus high diphosphate levels and a high AMP-to-ATP ratio support the operation of the enzyme in the acetate-forming direction, generating ATP. The GABA shunt II pathway describes a route that allows the cyanobacterium Synechocystis sp. PCC 6803 to convert 2-oxoglutarate to succinate, closing an otherwise incomplete TCA cycle. We also updated the pyruvate fermentation to acetate V pathway, which was previously known to occur only in trypanosomatids and some parasitic helminths, to reflect the recent discovery of the pathway in a bacterium.

• acetate and ATP formation from acetyl-CoA III
• GABA shunt II
• pyruvate fermentation to acetate V

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of February 2022) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6621 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 25.5

MetaCyc KB Statistics

Pathways	2980
Reactions	17509
Enzymes	13540
Chemical Compounds	17656
Organisms	3325
Citations	70088
EC numbers	6560
Textbook Page Equivalency	10757

Released on December 15, 2021

New and Updated Pathways

We have added 11_{[more info]} new pathways to MetaCyc since the last release.

Helicobacter pylori metabolism

Helicobacter pylori is a Gram-negative bacterium that is often found in the human stomach. It is estimated that more than 50% of the world's population is colonized by the bacterium. However, in 10-20% of the cases an infection results in gastritis (stomach inflammation) or ulcers, and in some cases the infection may lead to the development of certain cancers.

The complete genome and metabolic network of Helicobacter pylori 26695 is now available in a newly curated Tier 2 BioCyc database.

We have added several pathways describing the biosynthesis of the unique lipopolysaccharide (LPS) of this pathothogen, which contains Lewis (Le) antigens, structures found on human epithelial and cancer cells. These structures allow the organism to evade innate and adaptive immune responses.

Another H. pylori pathway describes a variant of tetrahydrofolate biosynthesis that does not include EC 1.5.1.3, dihydrofolate reductase. This pathway variant is found in organisms that possess EC 2.1.1.148, thymidylate synthase (FAD) (ThyX) instead of the more common EC 2.1.1.45, thymidylate synthase (ThyA). Unlike ThyA, which produces 7,8-dihydrofolate, ThyX forms tetrahydrofolate, and thus organisms that possess it do not need EC 1.5.1.3 to restore 7,8-dihydrofolate back to tetrahydrofolate.

• lipid IV_A biosynthesis (H. pylori)
• Kdo transfer to lipid IV_A (H. pylori)
• (Kdo)₂-lipid A biosynthesis (H. pylori)
• (Kdo)₂-lipid A modification (H. pylori)
• lipid A-core biosynthesis (H. pylori)
• H. pylori 26695 O-antigen biosynthesis
• tetrahydrofolate biosynthesis II

Degradation Pathways

The TCA cycle intermediate fumarate can react spontaneously with thiol-containing nucleophiles such as cysteine and glutathione to form S-(2-succinyl)-adducts. A new pathway described from Bacillus subtilis enables the organism to detoxify these compounds and use them as a sulfur source.

• S-(2-succinyl)-L-cysteine degradation

Inulin is a type of fructan - a polysaccharide composed of D-fructose chains attached to a terminal glucose. The fructose units in inulins are joined by a β(2→1) glycosidic bond. This new pathway describes the degradation of inulin via difructose anhydride III (DFA III), a low-calories sugar substitute with commercial potential.

• inulin degradation

Fucose is a common sugar, found in N-linked glycans on mammalian, insect and plant cell surfaces, in many bacterial glycans, and in other biomolecules. It has been shown to be metabolized via two pathway variants, one leading to formation of (S)-lactaldehyde, while the other forms pyruvate and (S)-lactate. We have now added the second variant, which was originally described from pig liver, and has been characterized in detail from several bacterial species.

• L-fucose degradation II

Biosynthetic Pathways

Cyclobis-(1→6)-α-nigerosyl, also known as cycloalternan, is a cyclic glucotetraose with alternate α(1→6)- and α(1→3)-glucosidic linkages, produced by several bacterial species during the degradation of complex glycans. The compound is formed extracellularly, and is degraded after its import into the cell.

• cyclobis-(1→6)-α-nigerosyl biosynthesis

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of October 2021) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6560 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 25.1

MetaCyc KB Statistics

Pathways	2969
Reactions	17412
Enzymes	13461
Chemical Compounds	17572
Organisms	3327
Citations	68779
EC numbers	6563
Textbook Page Equivalency	10668

Released on Aug 5, 2021

New and Updated Pathways

We have added 32_{[more info]} new pathways to MetaCyc since the last release and revised 17 pathways by modifying pathway diagrams, adding commentary, or updating enzyme and gene information. We also updated two superpathways, for a total of 51 new and updated pathways.

Central Metabolism Pathways

The reductive glycine pathway is a novel route for carbon dioxide fixation, which has been described in the bacteria Clostridium drakei and Desulfovibrio desulfuricans. The pathway involves some of the enzymes of the Wood-Ljungdahl pathway together with EC 1.4.1.27, the glycine cleavage system, and  EC 1.21.4.2, glycine reductase, and afford fixation of three CO₂ molecules. Another new pathway describes the removal of lower ligands from cobamides and attachment of a different one - a phenomenon known as cobamide remodeling.

• reductive glycine pathway
• adenosylcobinamide-GDP salvage from assorted adenosylcobamides

Degradation Pathways

Carbofuran is one of the most toxic broad-spectrum and systemic N-methyl carbamate pesticides and is used extensively as an insecticide, nematicide and acaricide for agricultural, domestic and industrial purposes. It is highly toxic to mammals, birds, and honeybees, and has a moderate to high toxicity to most aquatic organisms. We added three pathways that describe bacterial degradation of the compound. We also added two pathways that describe the degradation of methoxylated aromatic compounds, which are common in the environment as breakdown products of lignin; a third variant of L-carnitine degradation described from the acetogenic gut bacterium Eubacterium limosum; and a degaradation pathway found in axillary (underarm) bacteria that produces 3-methyl-3-sulfanylhexan-1-ol, one of the compounds that give human sweat its distinctive odour. In addition, our EcoCyc curators have submitted two new pathways describing the degradation of L-aspartate under aerobic and anaerobic conditions.

• carbofuran degradation I
• carbofuran degradation II
• carbofuran degradation III
• L-aspartate degradation II (aerobic)
• L-aspartate degradation II (anaerobic)
• methoxylated aromatic compound degradation I
• methoxylated aromatic compound degradation II
• S-(6-hydroxy-4-methylhexan-4-yl)-L-cysteinylglycine degradation

Biosynthetic Pathways

4-Aminobenzoate is an important metabolic intermediate, leading to the biosynthesis of various products such as folates, ubiquinone (in eukaryotes), and various bacterial antibiotics (e.g., candicidins). We added two new variants describing its biosynthesis. A new pathway describes NAD biosynthesis under anaerobic conditions, where fumarate serves as an alternative electron acceptor to dioxygen. Two new pathways describe the biosynthesis of the fatty acids palmitate and stearate in organisms that use an NADPH-dependent enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.104) instead of the more common NADH-dependent enzyme (EC 1.3.1.9).

• 4-aminobenzoate biosynthesis II
• 4-aminobenzoate biosynthesis III
• NAD de novo biosynthesis IV (anaerobic)
• palmitate biosynthesis III
• stearate biosynthesis IV

Lipid A Biosynthesis

Lipid A is a lipid component of the lipopolysaccharides (LPS) of Gram-negative bacteria. Its hydrophobic nature allows it to anchor the LPS to the outer membrane. Different bacterial species often produce lipid A molecules differing in their structure. However, since historically the lipid A from Escherichia coli was the first one to be studied in detail, the Enzyme Commission (EC) definitions of the enzymes involved have been crafted to be specific for the E. coli structure. Very recently the Enzyme Commission has revised those definitions to provide a more generic description that applies to the majority of Gram-negative bacteria. To reflect these changes, we have created a new set of pathways that describe the biosynthesis of a generic lipid A molecule. In addition we added  a pathway that describes the formation of the lipidA-core structure in Salmonella strains.

• (Kdo)₂-lipid A biosynthesis (generic)
• Kdo transfer to lipid IV_A (generic)
• lipid IV_A biosynthesis (generic)
• lipid A-core biosynthesis (Salmonella)

Secondary Metabolism Pathways

6-Diazo-5-oxo-L-norleucine (DON) is the best-studied broadly active L-glutamine (Gln) antagonist, and is used extensively as an inhibitor of enzymes that act on Gln, such as EC 3.5.1.2, glutaminase. DON contains an unusual N=N double bond, which is formed by a diazotase enzyme using nitrite, which in turn is produced from L-aspartate. We added new pathways describing the formation of nitrite, DON, and the further processing of DON into the tripeptide alazopeptin, which has anticancer and antitrypanosomal activities. Nitrite is also used for formation of an N=N double bond during the biosynthesis of cremeomycin, an antibiotic formed by Streptomyces cremeus. Other enzymes capable of forming N-N bonds participate in the pathways for L-piperazate and streptozotocin biosynthesis. Another new pathway describes the formation of trimethylamine N-oxide by a deep ocean bacterium, in which the compound acts as a piezolyte, stabilizing intracellular proteins and cell structure for their survival under the high hydrostatic pressure of the deep ocean.

• 6-diazo-5-oxo-L-norleucine biosynthesis
• alazopeptin biosynthesis
• cremeomycin biosynthesis
• L-piperazate biosynthesis
• nitrite biosynthesis
• streptozotocin biosynthesis
• trimethylamine N-oxide biosynthesis

Archaeal Metabolism

A new methanogenesis pathway describes the formation of methane from methoxylated aromatic compounds, which are produced by degradation of lignin. Another archaeal pathway describes the formation of the thiazole component of thiamine diphosphate by an enzyme highly similar to the suicide enzymes found in plants and fungi, yet capable of catalyzing multiple catalytic rounds.

• methanogenesis from methoxylated aromatic compounds
• thiazole component of thiamine diphosphate biosynthesis IV

Eukaryotic Pathways

The pathway listed below partially describes the formation of S-(6-hydroxy-4-methylhexan-4-yl)-L-cysteinylglycine, a major component of human axillary (underarm) secretion. Even though the compound is odourless, it is broken down by bacteria as described above (see S-(6-hydroxy-4-methylhexan-4-yl)-L-cysteinylglycine degradation), producing the highly odoriferous compound 3-methyl-3-sulfanylhexan-1-ol.

• S-(6-hydroxy-4-methylhexan-4-yl)-L-cysteinylglycine biosynthesis

Phage Pathways

The genomes of certain phages do not contain adenine bases. Instead, those genomes contain the nucleotide base 2,6-diaminopurine (Z), which confers resistance to all restriction enzymes whose recognition sequence involves adenine. A new pathway describes the biosynthesis of this unique nucleotide.

• dZTP biosynthesis

Other New Pathways

The pathway below describes how D-cycloserine, an antibiotic substance produced by several Streptomyces species, prevents the catalytic activities of some pyridoxal 5'-phosphate-dependent enzymes by displacing the cofactor and interacting with it.

• D-cycloserine inhibition of pyridoxal 5'-phosphate

Revised Pathways

We have redrawn the structures of all of our peptidoglycan-related compounds and altered the pathways to make the the pathways more uniform and the complex topic of peptidoglycan biosynthesis easier to understand.

• peptidoglycan biosynthesis II (staphylococci)
• peptidoglycan biosynthesis III (mycobacteria)
• peptidoglycan biosynthesis IV (Enterococcus faecium)
• peptidoglycan biosynthesis V (β-lactam resistance)
• peptidoglycan cross-bridge biosynthesis I (S. aureus)
• peptidoglycan cross-bridge biosynthesis II (E. faecium)
• peptidoglycan cross-bridge biosynthesis III (Enterococcus faecalis)

We have modifed several pathways that describe the biosynthesis of common glycosaminoglycans to provide a consistent and more easily undserstandable format, based on glycan icons.

• chondroitin biosynthesis
• chondroitin sulfate biosynthesis
• dermatan sulfate biosynthesis
• heparan sulfate biosynthesis
• superpathway of chondroitin sulfate biosynthesis
• superpathway of dermatan sulfate biosynthesis

Other pathways that were revised to reflect new information or to improve their accuracy and delivery of information include the following.

• chitobiose degradation
• equisetin biosynthesis
• lipoprotein posttranslational modification
• sch210971 and sch210972 biosynthesis
• TCA cycle V (2-oxoglutarate synthase)
• uracil degradation III

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of July 2021) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6563 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 25.0

MetaCyc KB Statistics

Pathways	2937
Reactions	17310
Enzymes	13356
Chemical Compounds	17314
Organisms	3295
Citations	68305
EC numbers	6492
Textbook Page Equivalency	10544

Released on May 19th, 2021

New and Updated Pathways

We have added 85_{[more info]} new pathways to MetaCyc since the last release and revised 15 pathways by modifying pathway diagrams, adding commentary, or updating enzyme and gene information. We also added two superpathways, for a total of 102 new and updated pathways.

O Antigen Biosynthesis

O antigens are one of the three components of lipopolysaccharides (LPS), which are one of the major structural and immunodominant molecules of the outer membrane in Gram-negative bacteria. The O antigens are polysaccharides that extend away from the cell surface, consisting of a polymer of an oligosaccharide repeating unit normally containing two to eight sugar residues. The composition and structure of the O-antigen determines the sero-type of the organism. Serotyping is a highly useful technique for identifying strains that vary in host range and disease spectrum. During this release period we curated pathways for the biosynthesis of O antigens of the remaining Salmonella enterica serotypes (we now have full coverage of the O antigens produced by this species), of many Escherichia coli serotypes, and some O antigens produced by Brucella abortus, Porphyromonas gingivalis, and Shigella boydii.

• Brucella abortus O antigen biosynthesis
• Escherichia coli serotype O:107 O antigen biosynthesis
• Escherichia coli serotype O:111/Salmonella enterica serotype O:35 O antigen biosynthesis
• Escherichia coli serotype O:117 O antigen biosynthesis
• Escherichia coli serotype O:127 O antigen biosynthesis
• Escherichia coli serotype O:128 O antigen biosynthesis
• Escherichia coli serotype O:149/Shigella boydii serotype O1 O antigen biosynthesis
• Escherichia coli serotype O:15 O antigen biosynthesis
• Escherichia coli serotype O:152 O antigen biosynthesis
• Escherichia coli serotype O:157/Salmonella enterica serotype O:30 O antigen biosynthesis
• Escherichia coli serotype O:169 O antigen biosynthesis
• Escherichia coli serotype O:177 O antigen biosynthesis
• Escherichia coli serotype O:183/Shigella boydii serotype O:10 O antigen biosynthesis
• Escherichia coli serotype O:1B/Salmonella enterica serotype O:42 O antigen biosynthesis
• Escherichia coli serotype O:2 O antigen biosynthesis
• Escherichia coli serotype O:21/Salmonella enterica serotype O:38 O antigen biosynthesis
• Escherichia coli serotype O:49 O antigen biosynthesis
• Escherichia coli serotype O:50 O antigen biosynthesis
• Escherichia coli serotype O:51/Salmonella enterica serotype O:57 O antigen biosynthesis
• Escherichia coli serotype O:52 O antigen biosynthesis
• Escherichia coli serotype O:55/Salmonella enterica serotype O:50 O antigen biosynthesis
• Escherichia coli serotype O:56 O antigen biosynthesis
• Escherichia coli serotype O:7 O antigen biosynthesis
• Escherichia coli serotype O:71/Salmonella enterica serotype O:28ac O antigen biosynthesis
• Escherichia coli serotype O:77/Salmonella enterica serotype O:6,14 O antigen biosynthesis
• Escherichia coli serotype O:8 O antigen biosynthesis
• Escherichia coli serotype O:85/Salmonella enterica serotype O:17 O antigen biosynthesis
• Escherichia coli serotype O:9 O antigen biosynthesis
• Porphyromonas gingivalis W50 O-LPS antigen biosynthesis
• Salmonella enterica serotype O:13 O antigen biosynthesis
• Salmonella enterica serotype O:18 O antigen biosynthesis
• Salmonella enterica serotype O:39 O antigen biosynthesis
• Salmonella enterica serotype O:54 O antigen biosynthesis
• Salmonella enterica serotype O:6,7 O antigen biosynthesis
• Shigella boydii serotype 6 O antigen biosynthesis

We also revised the following existing pathways:

• Escherichia coli serotype O:104 O antigen biosynthesis
• Escherichia coli serotype O:9a O antigen biosynthesis

Lipid A and Core Oligosaccharide Biosynthesis

The other two components of the lipopolysaccharides of Gram-negative bacteria (in addition to the O antigens) are lipid A and the core oligosaccharide. The hydrophobic lipid A serves to anchor the LPS to the outer membrane. The core oligosaccharides are conceptually divided into two regions: inner core and outer core. The inner core, which is attached to lipid A, is more conserved among species, often contains 3-deoxy-α-D-manno-2-octulosonate (Kdo) and L-glycero-D-manno-heptose (Hep) residues, and is often phosphorylated. It plays a critical role in the essential barrier function of the outer membrane. The outer core often comprises a multi-hexose backbone modified with varying side-branch substitutions of hexose and acetamidohexose residues. The outer core also serves as the attachment site for the O antigen. We have added several pathways that describe the biosynthesis of these components in Brucella species and in P. gingivalis.

• (Kdo)₂-lipid A biosynthesis (P. gingivalis)
• (Kdo)₂-lipid A biosynthesis I (Brucella)
• Kdo transfer to lipid IV_A (P. gingivalis)
• Kdo transfer to lipid IV_A IV (Brucella)
• lipid A-core biosynthesis (Brucella)
• lipid A-core biosynthesis (P. gingivalis)
• lipid IV_A biosynthesis (2,3-diamino-2,3-dideoxy-D-glucopyranose-containing)
• lipid IV_A biosynthesis (P. gingivalis)

Other Polysaccharide-Related Biosynthetic Pathways

We created a new pathway for the biosynthesis of colanic acid, an exopolysaccharide secreted by E. coli and a number of other Enterobacteriaceae that encapsulates the organism, resulting in a mucoid appearance. We also revised our existing pathway for the biosynthesis of succinoglycan, an exopolisaccharide produced by the nitrogen-fixing plant symbiont Sinorhizobium meliloti that is required for the invasion of plant root nodules, and added a superpathway for the biosynthesis of the enterobacterial common antigen (ECA), an outer membrane glycolipid shared by all members of the Enterobacteriaceae.

• colanic acid (Escherichia coli K12) biosynthesis
• succinoglycan biosynthesis
• superpathway of enterobacterial common antigen biosynthesis

Many polysaccharides contain unusual, modified sugar residues. We created several pathways that describe the biosynthesis of some of these less common sugars. As a rule, sugar building blocks of polysaccharides are synthesized in their activated nucleotide diphosphate forms.

• GDP-N-acetyl-α-D-perosamine biosynthesis
• GDP-N-formyl-α-D-perosamine biosynthesis
• UDP-3-acetamido-2,3-dideoxy-2-(seryl)amino-α-D-glucuronamide biosynthesis
• UDP-3-acetamido-2-amino-2,3-dideoxy-α-D-glucopyranose biosynthesis

Arsenic Metabolism

Arsenic is a natural component of the earth's crust and is widely distributed throughout the environment in the air, water and land. It exists most commonly in the (III) and (V) oxidation states, and many compounds of both forms are highly toxic. All organisms have developed defense mechanisms to cope with arsenic compounds. In this release we performed an extensive revision of our coverage of arsenic compound metabolism. We have added 11 new pathways  and revised 5 existing pathways. The pathways cover arsenic metabolism in bacteria, yeast, plants and animals.

• arsenate detoxification I
• arsenate detoxification III
• arsenic detoxification (plants)
• arsenite methylation (bacterial)
• methylarsonous acid detoxification I
• methylarsonous acid detoxification II
• methylarsonous acid detoxification III
• roxarsone (and nitarsone) degradation III
• roxarsone (and nitarsone) degradation IV
• roxarsone degradation I
• roxarsone degradation II

The following pathways have been revised:

• arsenate detoxification V
• arsenic detoxification (mammals)
• arsenic detoxification (yeast)
• arsenite to oxygen electron transfer
• arsenite to oxygen electron transfer (via azurin)

Central Metabolism

We have added a new variant of the TCA cycle found in members of the pathogenic Chlamydia genus. These organisms lack several key enzymes of the canonical TCA cycle, and possess a truncated pathway that does not involve acetyl-CoA. The main input to this pathway variant is 2-oxoglutarate, which is derived from L-glutamate acquired from the host. Another pathway describes the conversion of pyruvate to acetyl-CoA by EC 1.2.7.1, pyruvate synthase. The conversion of pyruvate to acetyl-CoA is a key step linking the glycolysis pathway with the TCA cycle. While most organisms utilize the pyruvate dehydrogenase system for this purpose, in some organisms, such as the human gut bacterium Faecalibacterium prausnitzii, this conversion is only carried out by pyruvate synthase.

• pyruvate decarboxylation to acetyl CoA III
• TCA cycle VIII (Chlamydia)

Sterol Metabolism

We have added yet another cholesterol biosynthesis pathway. This one comes from diatoms and involves a mix of enzymes known from plants, fungi, and animals. We also added a pathway describing how diatoms synthesize a different set of sterols, and created a superpathway that integrates these two pathways.

• 24-epi-campesterol, fucosterol, and clionasterol biosynthesis (diatoms)
• cholesterol biosynthesis (diatoms)
• superpathway of sterol biosynthesis in diatoms

Vitamin and Cofactor Metabolism

4-aminobenzoate is a precursor of several important compounds, including tetrahydrofolate (THF). We added a new pathway variant that described its biosynthesis in some Gram-positive bacteria such as Bacillus subtilis. The enzyme cofactor biotin is produced via the precursor (8S)-8-amino-7-oxononanoate. We added a new pathway variant for the biosynthesis of this precursor, which is found in the α proteobacteria.

• 4-aminobenzoate biosynthesis II
• 8-amino-7-oxononanoate biosynthesis IV

Degradation Pathways

A new pathway described the degradation of 6-sulfo-D-quinovose by Gram-positive bacteria. Two new pathways describe the degradation of the compound popularly known as 3-sulfopropanediol [it's correct name is (2S)-2,3-dihydroxypropane-1-sulfonate], which is produced during the degradation of 6-sulfo-D-quinovose. We also added new pathway variants for the degradation of D-mannose and methylglyoxal, respectively, and a pathway for the fermentation of pyruvate to (R)-lactate. We modified the acetoin degradation pathway to show the contribution of the individual components of the acetoin dehydrogenase system, making it consistent with pathways showing similar enzyme systems (such as the pyruvate dehydrogenase system),  and revised our daidzin and daidzein degradation pathway to reflect current knowledge.

• 3-sulfopropanediol degradation II
• 3-sulfopropanediol degradation III
• D-mannose degradation II
• methylglyoxal degradation VIII
• pyruvate fermentation to (R)-lactate
• sulfoquinovose degradation III
• acetoin degradation
• daidzin and daidzein degradation

Bile Acid Epimerization

During the processing of bile acids by gut bacteria the hydroxyl groups at the 3, 7 and 12 positions are often epimerized from α to β configuration via stable oxo intermediates. Each epimerization event requires two enzymes - one for the conversion of the α hydroxyl to an oxo group, and the other for the conversion of the oxo group to the β hydroxyl. Since different organisms have different sets of epimerizing enzymes, we have created a set of three separate pathways to describe these processes.

• bile acids 12-O-epimerization
• bile acids 3-O-epimerization
• bile acids 7-O epimerization

Electron Transport in Cyanobacteria

EC 7.1.1.10, ferredoxin—quinone oxidoreductase (H⁺-translocating) is a key enzyme in the electron transfer chain of cyanobacteria and plastids that until recently has been mischaracterized. The enzyme is very similar to the bacterial/mitochondrial NADH:ubiquinone reductase (H⁺-translocating) (EC 7.1.1.2), and was presumed to catalyze a similar reaction. However, it is now well established that the enzyme interacts with ferredoxin rather than NADH. The enzyme couples electron transport from ferredoxin to plastoquinone with proton pumping from the cytoplasm to the thylakoid lumen, and participates in cyclic electron flow, retuning electrons generated by photosystem I to the plastoquinone pool, thus bypassing the generation of reducing power. It may also participate in respiration using electrons originating from NADPH via the action of EC 1.18.1.2, ferredoxin—NADP⁺ reductase (FNR), operating in the direction of ferredoxin reduction. Based on the new functional characterization of the enzyme we have revised several cyanobacterial electron transport pathways and created a new pathway to describe cyclic electron flow.

• cyclic electron flow
• NADPH to cytochrome c oxidase via plastocyanin
• succinate to chytochrome c oxidase via cytochrome c₆
• succinate to cytochrome c oxidase via plastocyanin
• succinate to plastoquinol oxidase

Secondary Metabolite Biosynthesis

Pyrrolomycins are a group of polyhalogenated metabolites produced by Streptomyces species whose structures include a dichloro-pyrrole moiety linked to a halogenated-hydroxyphenyl ring via a one-carbon bridge. Some of the pyrrolomycins have powerful biological activities (e.g anthelmintic, neuropeptide-activity modulatory, and antistaphylococcal). A new pathway describes their biosynthesis. Strychnine is a terpene indole alkaloid produced by plants of the Strychnos genus. It is a powerful toxin (a lethal dose of strychnine for an adult human is in the range of 30-100 mg) due to it being an antagonist of glycine and acetylcholine receptors affecting primarily the motor nerve fibers in the spinal cord. Much is still unknown about the biosynthesis of strychnine, but the new pathway summarizes what is currently known. Three revised pathways describe the latest available information about the biosynthesis of cinchona alkaloids (a group of alkaloids occurring in the bark of cinchona trees, the most famous of which is quinine); clavulanate (an antibiotic produced by Streptomyces clavuligerus that is used clinically in combination with β-lactam antibiotics to combat resistance in bacterial pathogens); and steviol (the aglycone precursor of the sweet compounds produced by the plant Stevia rebaudiana).

• pyrrolomycin biosynthesis
• strychnine biosynthesis
• cinchona alkaloids biosynthesis
• clavulanate biosynthesis
• steviol biosynthesis

Other Eukaryotic Pathways

A new pathway describes the biosynthesis of 11-oxygenated C19 steroids (11-oxyandrogens). These steroids have been long identified and recognized as major androgens in teleost fishes. Much more recently it has been discovered that they are also produced in humans and play an important role in several disorders such as congenital adrenal hyperplasia (CAH), polycystic ovary syndrome (PCOS), and premature adrenarche. Other new pathways include a dTMP biosynthesis pathway that is unique to mitochondria, a palmitoleate biosyntesis pathway variant found in fungi and animals, and a pathway for the biosynthesis of xanthommatin, the predominant pigment in arthropods and cephalopods, which absorbs UV-vis light and changes its color depending on the environment.

• 1-oxyandrogens biosynthesis
• dTMP de novo biosynthesis (mitochondrial)
• palmitoleate biosynthesis IV (fungi and animals)
• xanthommatin biosynthesis

Additional Revised Pathways

We have revised an L-methionine biosynthesis pathway that is found in methanogenic archaea and some bacteria, and updated an existing pathway that describes N-glycosylation of bacterial proteins to include the flippase reaction, which exports the assembled oligosaccharide from the cytoplasm to the periplasm, where it is attached to the target protein.

• L-methionine biosynthesis IV
• protein N-glycosylation (bacterial)

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of March 2021) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6492 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 24.5

MetaCyc KB Statistics

Pathways	2859
Reactions	16986
Enzymes	12992
Chemical Compounds	16861
Organisms	3185
Citations	65725
EC numbers	6410
Textbook Page Equivalency	10179

Released on January 7th, 2021

New and Updated Pathways

We have added 11_{[more info]} new pathways to MetaCyc since the last release and revised 4 pathways by modifying pathway diagrams, adding commentary, or updating enzyme and gene information, for a total of 15 new and updated pathways.

Salmonella O antigen biosynthesis

O antigens are one of the three components of lipopolysaccharides (LPS), which are one of the major structural and immunodominant molecules of the outer membrane in Gram-negative bacteria. The O antigens are polysaccharides that extend away from the cell surface, consisting of a polymer of an oligosaccharide repeating unit normally containing two to eight sugar residues. The composition and structure of the O-antigen determines the sero-type of the organism. Serotyping  is a highly useful technique for identifying strains that vary in host range and disease spectrum. During this release period we curated pathways for the biosynthesis of seven of the most common O antigens of Salmonella, which are found in members of groups A, B, C2, D1, D2, D3 and E.

• group A Salmonella O antigen biosynthesis
• group B Salmonella O antigen biosynthesis
• group C2 Salmonella O antigen biosynthesis
• group D1 Salmonella O antigen biosynthesis
• group D2 Salmonella O antigen biosynthesis
• group D3 Salmonella O antigen biosynthesis
• group E Salmonella O antigen biosynthesis

Eukaryotic Pathways

Androgens are steroid hormones that stimulate or control the development and maintenance of male characteristics in vertebrates, including the activity of the accessory male sex organs and development of male secondary sex characteristics, by binding to androgen receptors. Testosterone is the major androgen in adult males, and is formed mostly in the testes. 5α-dihydrotestosterone (DHT) plays a crucial role in utero, triggering differentiation of the male sex organs, and continues to play an important role in the prostate of the adult. DHT is synthesized in peripheral tissue such as the prostate by the 5α-reduction of testosterone, with little amounts of DHT found in the circulation. Relatively recently an additional pathway for the generation of DHT, which does not involve testosterone, has been discovered. This pathway may hold important clues for future treatment of prostate cancer.

• backdoor pathway of androgen biosynthesis

Analysis of sterol metabolites in the red alga Chondrus crispus did not find evidence for several of the intermediates of the plant cholesterol biosynthetic pathway, and detected several other sterols not produced by plants. A new pathway explains the production of the observed intermediates and the lack of those not observed.

• cholesterol biosynthesis (algae, late side-chain reductase)

Cellular dTTP levels need to be tightly controlled for efficient DNA replication in the cell nucleus and mitochondria. Studies to elucidate how mitochondria maintain their dTTP levels have led to the discovery of a novel de novo dTMP biosynthetic pathway unique to mitochondria.

• dTMP de novo biosynthesis (mitochondrial)

Some microorganisms import the sugar mannose using a phosphoenolpyruvate (PEP)-dependent sugar transporting phosphotransferase system (PTS) in a transport reaction that involves the phosphorylation of the sugar. Other organisms import the sugar in its unphosphorylated form. In such organisms subsequent degradation proceeds by phosphorylation, followed by isomerization to the common central metabolite β-D-fructofuranose 6-phosphate.

• D-mannose degradation II

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of October 2020) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6467 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 24.1

MetaCyc KB Statistics

Pathways	2847
Reactions	16810
Enzymes	12943
Chemical Compounds	16631
Organisms	3161
Citations	65725
EC numbers	6469
Textbook Page Equivalency	10111

Released on September 8th, 2020

New and Updated Pathways

We have added 48_{[more info]} new pathways and one superpathway to MetaCyc since the last release. In addition, we significantly revised 31 pathways and one superpathway by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 81 new and updated pathways.

Fatty Acid Metabolism

Many Gram-positive organisms, such as the bacilli, staphylococci, and streptomycetes, produce odd- and even-carbon-number branched-chain fatty acids. In Bacilus subtilis 95% of the total fatty acids are branched. Branched-chain fatty acids display a lower melting point temperature than their straight-chain equivalents, and their presence in the membrane is expected to increase its fluidity, similar to the effect of unsaturation. We added three new pathways that describe the biosynthesis of the different types of branched-chain fatty acids that are produced by fatty acid synthase complexes. Not all branched-chain fatty acids are produced this way -- we added a pathway for the biosynthesis of 10-methylstearate, a methyl-branched fatty acid found in mycobacteria that is produced from oleate by methyltransferases. We also added pathways describing the β-oxidation of 2-methyl-branched fatty acids by mitochondria, as well as the β-oxidation of valproate, a branched fatty acid that is used as a major drug in the treatment of epilepsy and in the control of several types of seizures.
Other additions in fatty acids metabolism include a new pathway for the biosynthesis of 9-decynoate, a terminal alkyne fatty acid produced by an intracellular symbiont of the mollusc known as "shipworm", as well as a revision of the complex pathway that leads to the biosynthesis of mycolic acids in mycobacteria. We also converted a pathway describing the formation of the mycolyl-arabinogalactan-peptidoglycan complex in these organisms to use glycan representation to simplify the presentation of these very large molecules.

• anteiso-branched-chain fatty acid biosynthesis
• even iso-branched-chain fatty acid biosynthesis
• odd iso-branched-chain fatty acid biosynthesis
• 10-methylstearate biosynthesis
• 2-methyl-branched fatty acid β-oxidation
• 9-decynoate biosynthesis
• mycolate biosynthesis
• mycolyl-arabinogalactan-peptidoglycan complex biosynthesis
• valproate β-oxidation
• superpathway of mycolate biosynthesis

Cytochrome c Biogenesis

The biogenesis of c-type cytochromes involves the covalent attachment of protoheme to two cysteines at a conserved CXXCH sequence in the apocytochrome peptide. Three unique cytochrome c assembly pathways, known as systems I, II, and III, have been described so far.

• cytochrome c biogenesis (system I type)
• cytochrome c biogenesis (system II type)
• cytochrome c biogenesis (system III type)

Stickland Reactions

Clostridium species such as Acetoanaerobium sticklandii can utilize certain combinations of amino acids for growth using Stickland reactions. These "reactions" (which are really pathways), named after their discoverer, L. H. Stickland, are fermentations of amino acid pairs in which one amino acid is oxidized and the other one is reduced. We added 8 new pathways describing this type of metabolism, and modified one existing pathway.

• L-alanine degradation V (oxidative Stickland reaction)
• L-alanine degradation VI (reductive Stickland reaction)
• L-arginine degradation XIII (reductive Stickland reaction)
• L-arginine degradation XIV (oxidative Stickland reaction)
• L-glutamate degradation XI (reductive Stickland reaction)
• L-isoleucine degradation III (oxidative Stickland reaction)
• L-leucine degradation V (oxidative Stickland reaction)
• L-proline degradation II (reductive Stickland reaction)
• L-valine degradation III (oxidative Stickland reaction)

Cofator Biosynthesis

We have added and revised several pathways describing the biosynthesis of enzyme cofactors. Many forms of molybdo- and tungsten-containing cofactors are known. Although they all derive from molybdopterin, they differ by attachment of different nucleotides and by modification of the number of oxo and sulfo groups attached to the metal. The pathways leading to their biosynthesis are not yet fully understood, and the new pathways describe current knowledge. The pathways describing the biosynthesis of molybdopterin and the molybdenum cofactor (MoCo) have been reorganized, and new pathways describe the sulfurylation of bis(guanylyl molybdopterin) cofactor and cytidylyl molybdenum cofactor, the formation of bis(tungstenpterin) cofactor and bis(guanylyl tungstenpterin) cofactor, and the formation of cytidylyl copper-molybdenum cofactor, a cofactor unique to EC 1.2.5.3, aerobic carbon monoxide dehydrogenase.
Among the roles of L-ascorbate is serving as a cofactor for many enzymes. We revised one of its biosynthetic pathways and added two more variants characterized from plants. We also added a salvage pathway that describes the formation of the cofactors FMN and FAD from riboflavin obtained from the environment, as well as a simple pathway that describes the formation of NADP from NAD.

• molybdopterin biosynthesis
• molybdenum cofactor biosynthesis
• bis(guanylyl molybdopterin) cofactor sulfurylation
• bis(guanylyl tungstenpterin) cofactor biosynthesis
• bis(tungstenpterin) cofactor biosynthesis
• cytidylyl copper-molybdenum cofactor biosynthesis
• cytidylyl molybdenum cofactor sulfurylation
• L-ascorbate degradation V
• L-ascorbate biosynthesis II (plants, L-gulose pathway)
• L-ascorbate biosynthesis VI (plants, myo-inositol pathway)
• L-ascorbate biosynthesis VII (plants, D-galacturonate pathway)
• flavin salvage
• NADP biosynthesis

Sulfur Compound Metabolism

We have revised a pathway describing sulfur oxidation that involves production of an intracellular sulfur intermediate, pathways describing the production and degradation of dimethylsulfoniopropanoate, and respiration using dimethylsulfide as the electron donor. A related new pathway describes the degradation of acrylate, which can be formed by cleavage of dimethylsulfoniopropanoate. Another new pathway describes the biosynthesis of thiocoraline, a thiodepsipeptide antitumor compound produced by two actinomycetes that possesses a strong antimicrobial activity against Gram-positive microorganisms and a potent cytotoxic activity.

• sulfur oxidation IV (intracellular sulfur)
• dimethylsulfide to cytochrome c₂ electron transfer
• dimethylsulfoniopropanoate biosynthesis II (Spartina)
• dimethylsulfoniopropanoate degradation II (cleavage)
• acrylate degradation II
• thiocoraline biosynthesis

Pathways of General Metabolism 

We have revised our description for the two segments of the pentose phosphate pathway (oxidative and non-oxidative), and added a new variant of the latter that does not involve EC 2.2.1.2, transaldolase. We also revised a eukaryotic pathway for the biosynthesis of glycine by the reverse action of the glycine cleavage complex, an L-proline biosynthesis pathway characterized from the cyanobacterium Nostoc sp. PCC 7120, and a ubiquinol-8 biosynthesis pathway that had been considered exclusively eukaryotic, but was recently found in the bacterium Xanthomonas campestris.

• pentose phosphate pathway (oxidative branch) I
• pentose phosphate pathway (non-oxidative branch) I
• pentose phosphate pathway (non-oxidative branch) II
• heme b biosynthesis V (aerobic)
• glycine biosynthesis II
• L-proline biosynthesis II (from arginine)
• ubiquinol-8 biosynthesis (late decarboxylation)

Degradation Pathways

Three new pathways describe the anaerobic degradation of cholesterol and testosterone, via androsrtendione. These challenging and complex pathways were studied mostly in the bacteria Sterolibacterium denitrificans and Steroidobacter denitrificans.
Other new degradation pathways describe the degradation of the D-amino acid D-phenylglycine and of phenylethanol, and revised pathways describe the degradation of L-arabinose and D-xylose.

• cholesterol degradation to androstenedione III (anaerobic)
• testosterone degradation (anaerobic)
• androsrtendione degradation II (anaerobic)
• D-phenylglycine degradation
• phenylethanol degradation
• D-xylose degradation III
• L-arabinose degradation III

Biosynthetic Bacterial Pathways

Lipopolysaccharides (LPS) are a major component of the outer membrane of Gram-negative bacteria. While they are protecting the membrane from certain kinds of chemical attacks, they also induce a strong response from animal immune systems. We have revised the pathway for enterobacterial common antigen biosynthesis and added a new pathway describing the biosynthesis of 6-deoxy-D-gulose, an unusual sugar found in the LPS of Yersinia enterocolitica type O:8.
A new large and complex pathway describes the biosynthesis of platensimycin, a potent and selective inhibitor of the elongation-specific condensing enzymes of type II fatty acid biosynthesis produced by Streptomyces platensis. Another complex pathway describes the biosynthesis of streptorubin B, a red pigmented antibiotic of the prodiginines family that is produced by some actinomycetes. We also created a new pathway variant for homospermidine biosynthesis and revised an existing variant.

• CDP-6-deoxy-D-gulose biosynthesis
• homospermidine biosynthesis II
• platensimycin biosynthesis
• serine racemization
• streptorubin B biosynthesis
• enterobacterial common antigen biosynthesis
• homospermidine biosynthesis I
• streptorubin B biosynthesis

Cyanobacterial Pathways

A new pathway describes aerobic respiration utilizing the NDH-1 (NADPH-quinone oxidoreductase) complex, plastoquinol, the cytochrome b₆f complex, plastocyanin, and the cytochrome aa₃-type cytochrome c oxidase. A revised pathway describes the metabolism of cyanophycin, an amino acid polymer that is found in most cyanobacteria.
Cyanophycin is composed of an L-aspartate backbone and L-arginine side groups, with typical size of 25-100 kDa, and serves as a temporary nitrogen reserve, which accumulates during the transition from the exponential- to the stationary-growth phase and disappears when balanced growth resumes.

• aerobic respiration (NDH-1 to cytochrome c oxidase via plastocyanin)
• cyanophycin metabolism

Plant-Specific Pathways

New plant pathways describe the biosynthesis of avenanthramides, a group of N-cinnamoylanthranilic acids that were shown to have anti-inflammatory, antioxidant, anti-itch, anti-irritant, and antiatherogenic activities; of geraniol in a Rosa hybrid cultivar; and of nerol in Glycine max (soybeans). We also revised the pathways for the steroidal glycoalkaloid α-tomatine, which is produced from cholesterol; carnosate, a benzenediol abietane diterpene synthesized by some members of the Lamiaceae family that has strong antioxidant, anti-inflammatory, and anticancer properties; and ephedrine, an aromatic amine synthesized by some members of the Ephedra genus that interacts with the adrenergic receptor system of humans, and is commonly used as stimulant, appetite suppressant, and decongestant. We also revised the VTC2 cycles, which produce β-L-galactose 1-phosphate for L-ascorbatwe biosynthesis.

• avenanthramide biosynthesis
• α-tomatine biosynthesis
• carnosate bioynthesis
• geraniol biosynthesis (cytosol)
• nerol biosynthesis
• ephedrine biosynthesis
• VTC2 cycle
• extended VTC2 cycle

Fungal Pathways

A new fungal pathway describes the biosynthesis of emodin, a compound produced by both fungi and plants that have laxative properties. Another new pathway describes the formation of geodin from emodin. Ibotenate and muscimol are compounds with strong psychoactive effects produced by Amanita muscaria, also known as the fly agaric mushroom. Ibotenate is an analog of the neurotransmitter L-glutamate and acts as a non-selective agonist of the NMDA and group I and II metabotropic glutamate receptors. Muscimol is an analog of 4-aminobutanoate (GABA), and is a potent, selective agonist for the GABA_A receptors. Omphalotin A is a cyclic peptide isolated from the basidiomycete Omphalotus olearius that shows strong and selective nematicidal activity against the plant pathogenic Meloidogyne incognita with no further phytotoxic, antibacterial, or antifungal activities. Finally, sterigmatocystin is an intermediate in the biosynthesis of the B-group and G-group aflatoxins, highly toxic and carcinogenic crop contaminants that create major economic and public health problems worldwide.

• emodin biosynthesis
• geodin biosynthesis
• ibotenate and muscimol biosynthesis
• omphalotin biosynthesis
• sterigmatocystin biosynthesis

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of August 2020) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6469 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 24.0

MetaCyc KB Statistics

Pathways	2801
Reactions	16456
Enzymes	12711
Chemical Compounds	16313
Organisms	3123
Citations	63952
EC numbers	6430
Textbook Page Equivalency	9789

Released on May 14, 2020

New and Updated Pathways

We have added 37_{[more info]} new pathways to MetaCyc since the last release. One of the new pathways was contributed by EcoCyc curator Ingrid Keseler. In addition, we significantly revised 12 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 49 new and updated pathways.

Degradation pathways

β-alanine is produced during the reductive degradation of pyrimidine nucleotides. A new pathway described in 2019, which is present in many Gram-positive bacteria, enables the organisms to recyle it, salvaging the nitrogen for protein biosynthesis. Another pathway discovered in 2019 enables bacteria to salvage the phosphorus from the phosphonate compound (2-trimethyl)aminoethylphosphonate, converting it to glycine betaine and orthophosphate. We also updated a pathway for the degradation of L-lysine found in Pseudomonads and a pathway for the degradation of thiocyanate by thiocyanate desulfurase, an enzyme that was isolated for the first time in 2020.

• β-alanine degradation III
• (2-trimethylamino)ethylphosphonate degradation
• L-lysine degradation V
• thiocyanate degradation I

S-methyl-5'-thioadenosine and 5'-deoxyadenosine are by-products produced by many enzymes the utilize S-adenosyl-L-methionine as a co-substrate. Recycling these products enables cells to reclaim not only the carbon skeleton, but also the sulfur and nitrogen they contain. Certain enzymes, originally discovered in the phototrophic bacteria Rhodospirillum rubrum and Rhodopseudomonas palustris, enable recycling of these compounds. A 2020 study identified orthologous enzymes in a number of pathogenic bacteria, including Bacillus anthracis, Clostridium tetani, and extra-intestinal pathogenic Escherichia coli strains.

• 5'-deoxyadenosine degradation I
• 5'-deoxyadenosine degradation II
• S-methyl-5-thio-α-D-ribose 1-phosphate degradation II
• S-methyl-5-thio-α-D-ribose 1-phosphate degradation III

Carbaryl is a carbamate insecticide commonly sold under the brand name Sevin. It interferes with the cholinergic nervous system of insects, resulting in muscle spasms and eventually death. Carbaryl-based insecticides are commonly used in the US for food crops, and carbaryl is also the active ingredient in Carylderm shampoo, which is used against head lice. However, carbaryl kills both targeted and beneficial insects (e.g., honeybees), as well as crustaceans. We added a pathway that describes the degradation of carbaryl by several Pseudomonas strains.

• carbaryl degradation

Glycine betaine and proline betaine are osmolytes, compounds that protect cells from osmotic pressure. We added pathways that describe their respective demethylation of these compounds by enzyme systems that transfer a methyl group, via a methyl-carrier corrinoid protein, to tetrahydrofolate.

• glycine betaine degradation III
• proline betaine degradation II

L-Dopa is used as a pro-drug for the neurotransmitter dopamine in the therapy of central nervous system disorders such as Parkinson's disease. To be effective, L-dopa needs to cross the blood-brain barrier before it is metabolized into dopamine, which cannot cross the barrier. We added a pathway that describes an interaction between two human gut microbiome members that results in conversion of L-dopa to 3-tyramine, rendering the treatment much less effective.

• L-dopa degradation II (bacterial)

Biosynthetic Pathways

Several new pathways describe the biosynthesis of enzyme cofactors. Factor 420 is mostly known from methanogenic archaea and Gram-positive bacteria. Recent findings defined the differences between the pathways found in these two types of organisms, leading to the creation of a new variant for the archaeal pathway. In addition, genome sequencing projects revealed that some Gram-negative bacteria had also acquired the genes. A new pathway describes the biosynthesis of a new variant of the cofactor, named 3PG-factor 420, in the Gram-negative bacterium Paraburkholderia rhizoxinica. Another new pathway describes the biosynthesis of the cofactor biotin using the novel enzyme BioU, which is found in haloarchaea and some cyanobacteria. Finally, a new pathway describes the biosynthesis of mycofactocin, a cofactor whose existence and biosynthetic pathway were predicted largely by bioinformatic analyses. Mycofactocin, which is found in a large number of species including pathogens such as Mycobacterium tuberculosis, is produced in a pathway somewhat similar to that of pyrroloquinoline quinone. A revised pathway describes the biosynthesis of aminopropanol phosphate, a precursor in the biosynthesis of adenosylcobinamide and adenosylcobyrate.

• 3PG-factor 420 biosynthesis
• aminopropanol phosphate biosynthesis I
• biotin biosynthesis from 8-amino-7-oxononanoate III
• factor 420 biosynthesis I (archaea)
• mycofactocin biosynthesis

The next group of pathways describes production of antibiotics or toxins. Colibactin is a genotoxic compound synthesized by some extraintestinal pathogenic and human gut commensal enterobacterial strains that interferes with the eukaryotic cell cycle. It induces DNA double-strand breaks, DNA cross-linking, chromosome aberrations, and cell cycle arrest, and has been linked to colorectal cancer. Its biosynthetic pathway is very complicated, but has been resolved in 2019. Lincomycin A is a lincosamide antibiotic that blocks protein synthesis in sensitive bacterial strains by inhibiting the peptidyltransferase reaction on the 50S ribosomal subunit. Much has been learned about its biosynthesis since the pathway was entered in MetaCyc in 2011, and we have now updated the pathway. Two new pathways describe the biosynthesis of ribosomal peptide natural products (RiPPs) - Microcin B17 is a gyrase inhibitor produced by Escherichia coli, while patellamide A and patellamide C are cytotoxic compounds produced by the cyanobacterium Prochloron didemni, a symbiont of the tunicate Lissoclinum patella. Ochratoxin A is a natural, toxic, secondary metabolite produced by several fungal species of the genera Penicillium and Aspergillus and is responsible for significant contamination of many types of foods, including cereal-based products, dry-cured foods, coffee, cocoa, spices, dried fruits, grapes, grape juice, must, and wine. Patulin is a polyketide metabolite produced by several types of molds that has immunological, neurological and gastrointestinal effects. It is the main mycotoxin contaminating apples. We have revised the pathway with new information obtained in the last 6 years. Another revised pathway is for the biosynthesis of dehydrophos, a phosponate-containing natrual product produced by Streptomyces luridus that exhibits broad spectrum antibiotic activity against both Gram-negative and Gram-positive bacteria.

• colibactin biosynthesis
• dehydrophos biosynthesis
• lincomycin A biosynthesis
• microcin B17 biosynthesis
• ochratoxin A biosynthesis
• patellamide A and C biosynthesis
• patulin biosynthesis

Thermophiles (both bacterial and archaeal) contain two types of unusual polyamines as major components of their polyamine pools. One type consists of long linear polyamines and the other consists of branched polyamines. We added pathways that describe the biosynthesis of both types.

• branched-chain polyamines biosynthesis
• long-chain polyamine biosynthesis

We have also added several pathways related to cell surface components. One pathway describes the biosynthesis of 6-Deoxy-D-gulose, an unusual sugar found in the lipopolysaccharide of the human and animal pathogen Yersinia enterocolitica (type O:8). Another pathway describes the biosynthesis of (2-aminoethyl)phosphonate-glycoconjugates. Most of the putative phosphonate biosynthetic gene clusters encode cell wall phosphonoglycans and phosphonolipids. Another pathway describes the biosynthesis of succinoglycan, which is produced by Sinorhizobium meliloti.

• CDP-6-deoxy-D-gulose biosynthesis
• cell-surface glycoconjugate-linked phosphonate biosynthesis
• succinoglycan biosynthesis

Cyanobacterial Pathways

Several of the new pathways are unique to cyanobacteria. One of these describes aerobic resipiration involving the NDH-2 complex. Unlike the large multiprotein complex NDH-1, NDH-2 is an NADH-oxidizing type II dehydrogenase consisting of a single subunit and presumably not contributing to a proton gradient across the membrane. Another pathway describes the transfer of electrons from photosystem II to the plastoquinol terminal oxidase (PTOX). This pathway is thought to function as a sink for a significant fraction of the photosynthetic electron transport under high irradiance. Two more pathways describe the biosynthesis of chlorophyll a₂ and chlorophyll b₂, divinyl forms of chlorophylls that are unique to members of the marine Prochlorococcus species.

• aerobic respiration in cyanobacteria (NDH-2 to cytochrome c oxidase via plastocyanin)
• chlorophyll a₂ biosynthesis
• chlorophyll b₂ biosynthesis
• protective electron sinks in the thylakoid membrane (PSII to PTOX)

Pathways of General Metabolism

New pathways that fall under this category include a sulfate reduction pathway that involves a ferredoxin-dependent assimilatory sulfite reductase; three pathways that describe the repair of NADH and NADPH hydrates, which function as inhibitors of several important dehydrogenases; a pathway that describes the formation and hydrolysis of polyphosphates; and a new variant of the mevalonate pathway that is found in most archaea. We also modified an existing pathway describing the mevalonate pathway in haloarchaea.

• assimilatory sulfate reduction IV
• NADH repair (prokaryotes)
• NADPH repair (eukaryotes)
• NADPH repair (prokaryotes)
• polyphosphate metabolism
• mevalonate pathway II (haloarchaea)
• mevalonate pathway IV (archaea)

Plant-Specific Pathways

A revised pathway describes the biosynthesis of curcuminoids, a class of diarylheptanoid secondary metabolites produced in turmeric and other related plant species. Another revised pathway describes the biosynthesis of N-hydroxy-L-pipecolate, is a signal molecule involved in Systemic Acquired Resistance (SAR), an immune response induced in the distal parts of plants following defense activation in local tissue.

• curcuminoid biosynthesis
• N-hydroxy-L-pipecolate biosynthesis

Other New Pathways

Additional new pathways include an arsenate detoxification pathway based on the ArsJ transporter, an MFS membrane protein that is specific for 1-arseno-3-phosphoglycerate; a new methanogenesis pathway from the common osmolyte glycine betaine; and two pathways that describe processing of bile acids by bacteria. The principal actions of gut bacteria on bile acids are C24 amide hydrolysis (deconjugation) and 7-dehydroxylation. One of the new pathways describes the deconjugation process, which removes the glycine and taurine moieties from conjugated bile acids; the other new pathway describes bile acid 7β-dehydroxylation, which is specific for ursodeoxycholate (most bile acids are processed by α-dehydroxylation, which is described in a revised pathway). Another revised pathway describes bile acids epimerization.

• arsenate detoxification V
• bile acid 7α-dehydroxylation
• bile acid 7β-dehydroxylation
• bile acids deconjugation
• bile acids epimerization
• 2-deoxy-D-glucose 6-phosphate degradation
• methanogenesis from glycine betaine

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of April 2020) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6430 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 23.5

MetaCyc KB Statistics

Pathways	2766
Reactions	16151
Enzymes	12564
Chemical Compounds	15935
Organisms	3067
Citations	62408
EC numbers	6377
Textbook Page Equivalency	9634

Released on Dec 18, 2019

New and Updated Pathways

We have added 18_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 10 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 28 new and updated pathways. We also added one superpathway.

Indole-3-acetate degradation: Indole-3-acetate ((indol-3-yl)acetate, IAA) is the main auxin hormone in plants, controlling many important physiological processes including cell enlargement and division, tissue differentiation, and responses to light and gravity. Some bacterial species are able to catabolize IAA. We have divided an existing pathway describing indole-3-acetate degradation into two different variant pathways and updated enzyme information.

• indole-3-acetate degradation I
• indole-3-acetate degradation II

Cobamide upper ligand biosynthesis: Cobamides are important cofactors of enzymes. They are corrinoids that contain upper and lower ligands. At least 16 different cobamides with structural variability in the lower ligand have been described from bacteria. During this release we created pathways that describe the biosynthesis of three of those lower ligands: 5-hydroxybenzimidazole, 5-methoxybenzimidazole, and 5-methoxy-6-methylbenzimidazole.

• 5-hydroxybenzimidazole biosynthesis (anaerobic)
• 5-methoxybenzimidazole biosynthesis (anaerobic)
• 5-methoxy-6-methylbenzimidazole biosynthesis (anaerobic)

Arsenate detoxification: Arsenate [As^VO₄^3-] is a structural analog of phosphate that inhibits phosphorylation processes. For example, ADP-arsenate spontaneously hydrolyzes, resulting in uncoupling of oxidative phosphorylation. Arsenite [As^III(OH)₃] is even more toxic, since it has a very high affinity for thiol groups, and thus binds to and inhibits many key enzymes that have thiol groups in their active sites. Unicellular organisms usually reduce arsenate to arsenite, which they extrude from the cell by specific arsenite efflux pump systems. In most mammals arsenic detoxification involves alternative steps of reduction and oxidative methylation. The end metabolites are methylarsonate, dimethylarsonite, and dimethylarsinate (cacodylate), which are less reactive than arsenate and arsenite, and are excreted in the urine. During this release we have created a new arsenate detoxification pathway (for thioredoxin-dependent arsenate reductases) and updated two existing ones.

• arsenate detoxification I (mammalian)
• arsenate detoxification II (glutaredoxin)
• arsenate detoxification III (thioredoxin)

Apiose and apionate degradation: D-Apiose is a unique branched-chain pentose found principally in plants. It is a key component of structurally complex cell wall polysaccharides such as rhamnogalacturonan-II (RG-II) in the cell walls of higher plants and in apigalacturonan in the cell walls of aquatic monocots, and is a building block of a large number of naturally occurring secondary metabolites. We have added two pathways for the degradation of D-apiose. One of those pathways leads to D-apionate, and we have also added three pathways describing the degradation of that compound.

• D-apiose degradation I
• D-apiose degradation II (to D-apionate)
• D-apionate degradation I (xylose isomerase family decarboxylase)
• D-apionate degradation II (RLP decarboxylase)
• D-apionate degradation III (RLP transcarboxylase/hydrolase)

Queuosine biosynthesis: Queuosine is a modified nucleoside that is present in certain tRNAs in bacteria and most eukaryotes (but not in yeast). Queuosine occupies the first anticodon position of tRNAs for L-histidine, L-aspartate, L-asparagine, and L-tyrosine. This anticodon position pairs with the third "wobble" position in codons, and queuosine improves accuracy of translation. The base component of queosine is called queuine. For this release we added two new pathways that describe the salvage of both queosine and queuine, which are used by organisms that cannot synthesize queosine.

• queuosine biosynthesis II (queuine salvage)
• queuosine biosynthesis III (queuosine salvage)

Archaeal pathways: We added a pathway for the biosynthesis of cyclic 2,3-bisphosphoglycerate, a compound involved in thermoadaptation in several thermophilic methanogenic genera of the archaea.

• cyclic 2,3-bisphosphoglycerate biosynthesis

Plant pathways: During this release we added a new pathway for the biosynthesis of crotonosine, a dienone alkaloid isolated from the plant Croton linearis (Spanish Rosemary), and revised several plant pathways. One revised pathway describes the biosynthesis of capsaicin, the most common of the capsaicinoids, which are alkaloids that are responsible for the pungency of chili peppers. Two revised pathways describe the biosynthesis of digitoxigenin and the cardenolide glycosides derived from it. The cardenolide glycosides are the main group of cardiac glycosides - plant-made compounds (mostly by members of the Digitalis genus, or Foxgloves) that have beneficial effects over patients with cardiac failure. Other revised biosynthesis pathways are for N-hydroxy-L-pipecolate, a key compound invovled in plant Systemic Acquired Resistance (SAR), and pyrethrin I, a natural insecticide extracted from the seed cases of Tanacetum cinerariifolium. We also revised the pathway that describes α-oxidation via (2R)-2-hydroperoxy fatty acids, which involves the enzyme fatty acid α-dioxygenase.

• capsaicin biosynthesis
• crotonosine biosynthesis
• cardenolide glucosides biosynthesis
• digitoxigenin biosynthesis
• fatty acid α-oxidation I (plants)
• N-hydroxy-L-pipecolate biosynthesis
• pyrethrin I biosynthesis

Other new pathways: A new pathway describes the biosynthesis of dipicolinate, a small polar molecule that accumulates to high concentrations in bacterial endospores (up to 25% of spore core dry weight) and is thought to play a role in spore heat resistance. Another new pathway describes the recycling of tetrahydropteridines, which serve as co-substrates for several monooxygenase enzymes, such as EC 1.14.16.2, tyrosine 3-monooxygenase and EC 1.14.16.7, phenylalanine 3-monooxygenase. During catalysis the co-susbtrate is hydroxylated by one of the atoms of dioxygen; the pathway describes how it is recycled back to its active form.

• dipicolinate biosynthesis
• tetrahydropteridine recycling

New Pathways from Plant Metabolic Network (PMN)

Two new pathways were contributed by PMN curators. The pathways describe similar transformations - the biosynthesis of the kavalactones (R)-(+)-kavain and yangonin from cinnamoyl-CoA and (E)-4-coumaroyl-CoA, respectively. The kavalactones are known for their psychoactive effects.

• kavain biosynthesis
• yangonin biosynthesis
• superpathway of kavalactone biosynthesis

Additional Revised Pathways

• L-phenylalanine degradation I (aerobic)

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of November 2019) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6377 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 23.1

MetaCyc KB Statistics

Pathways	2749
Reactions	16052
Enzymes	12482
Chemical Compounds	15819
Organisms	3046
Citations	61889
EC numbers	6349
Textbook Page Equivalency	9538

Released on Sept 19, 2019

New and Updated Pathways

We have added 27_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 12 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 39 new and updated pathways.

Fatty acid biosynthesis: There are two basic types of fatty acid biosynthesis systems, named type I and type II. Type I systems are found in lower eukaryotes and animals, while type II systems are found in bacteria, plants, parasites of the Apicomplexa phylum, and mitochondria. Thus, both systems operate in lower eukaryotes and animals - the type I system in the cytosol, and the type II system in the mitochondria. The main difference between the two systems is that type I systems consist of one or two large multifunctional gene products that form a single complex that contains all of the reaction centers required to produce a fatty acid, while in type II systems the different reactions are catalyzed by a series of individual soluble proteins. Each of these proteins is each encoded by a discrete gene, and the pathway intermediates are transferred between the proteinss as thioesters of an acyl-carrier protein. We rearranged our fatty acid initiation and extension pathways to make these distinctions clearer. The intermediates in the type I pathways are now shown bound to an [acp domain within a type I fatty acid synthase], while those in type II pathways are shown bound to an [acyl-carrier protein]. Two new pathways describe the initiation of fatty acids biosynthesis in animals and fungi by the type I and type II systems, which correspond to the cytoplasm and mitochondria, respectively. We have revised an existing pathway for the mitochondrial biosynthesis of octanoyl-[acyl-carrier protein], which is the precursor for (R)-lipoate biosynthesis. Another new pathway describes the extension of fatty acids by the mitochondial system to the level of myristate, which has been observed in the mold Neurospora crassa.

• fatty acid biosynthesis initiation (animals and fungi, cytoplasm)
• fatty acid biosynthesis initiation (mitochondria)
• myristate biosynthesis (mitochondria)
• octanoyl-[acyl-carrier protein] biosynthesis (mitochondria, yeast)

Degradation pathways: We added a pathway that describes the degradation of the organophosphorus insecticide chlorpyrifos, and a third variant of methylphosphonate degradation, characterized from the bacterium Gimesia maris. Other new pathways describe the oxidative degradation of glutarate (an intermediate of L-lysine degradation), the degradation of picolinate to fumarate, and a fourth variant for the degradation of sulfoacetaldehyde. A new pathway describes the fermentation of (S)-lactate, itself a common fermantation product, to propanoate, acetate, and hydrogen by members of the Veillonella genus, which are not able to utilize sugars.

• chlorpyrifos degradation
• glutarate degradation
• methylphosphonate degradation III
• (S)-lactate fermentation to propanoate, acetate and hydrogen
• sulfoacetaldehyde degradation IV

Lipid biosynthesis: A new pathway describes the biosynthesis of the glycine lipid N-[(3-palmitoyloxy)-palmitoyl]glycine. Glycine lipids are glycine-containing acyl-oxyacyl lipids that were observed in several members of the Bacteroides genus. We have also added several pathways that describe the biosynthesis of the four different forms of (Kdo)₂-lipid A that are found in Pseudomonas putida.

• glycine lipid biosynthesis
• (Kdo)₂-lipid A biosynthesis II (P. putida)
• Kdo transfer to lipid IV_A IV (P. putida)
• lipid IV_A biosynthesis (P. putida)

Factor 420 biosynthesis: Factor 420 (also known as F420 or coenzyme F420) is a redox-active compound well-known for its role in methanogenesis. While playing a crucial role in methanoarchaeal metabolism, F420 has also been found in various eubacteria of the actinobacteria class, such as Streptomyces, Rhodococcus, Nocardioides, and Mycobacterium, where it assists in the synthesis of antibiotics like tetracycline and lincomycin. In addition, a modified form of the compound is also used by cyanobacteria in the repair of DNA damage. Prior to 2019 the pathway was believed to start with (S)-lactate rather than phosphoenolpyruvate, resulting in incorrect activity assignments for EC 2.7.7.68 and EC 2.7.8.28 and some unassigned steps. The pathway was fully elucidated in 2019, and we have revised our pathway accordingly.

• factor 420 biosynthesis
• factor 420 polyglutamylation

Pyoverdine biosynthesis: Pyoverdines are a group of structurally related siderophores produced by fluorescent Pseudomonas species under iron starvation conditions. While many Pseudomonads make more than one type of siderophore molecules, pyoverdines are always the primary iron uptake system. We have significantly revised the existing pyoverdine biosynthesis pathway, adding the enzymes involved in the lower part of the pathway, which produce the four common forms glutamate-pyoverdine I, 2-oxoglutarate-pyoverdine I, succinamide-pyoverdine I, and succinate-pyoverdine I.

• pyoverdine I biosynthesis

Ursodeoxycholate biosynthesis: The pathway of ursodeoxycholate (UDCA) biosynthesis has been updated. Even though UDCA is chemically synthesized by multiple companies, several countries in East Asia, including China, South Korea, Laos, Vietnam, and Myanmar, still use "bile bears" - bears that are kept in captivity and used for harvesting their bile by surgery. Bear farming is extremely inhumane and many bears die of illness such as chronic infections and liver cancer. Despite being illegal in some of these countries, bear bile farming still exists in all of those countries and is a significant problem.

• ursodeoxycholate biosynthesis (bacteria)

Other biosynthetic pathways: A new pathway describes the biosynthesis of FAD-N5-oxide, a rare cofactor found in the proteins EncM of Streptomyces maritimus (involved in enterocin biosynthesis), RutA of Escherichia coli (involved in uracil catabolism) and DszA of Rhodococcus (involved in dibenzothiophene catabolism). Other pathways describe the biosynthesis of sodorifen, a volatile compound emitted by the rhizobacterium Serratia plymuthica that inhibits plant and fungal growth, and of methylphosphonate, which is produced by some marine bacteria and archaea. Phosphorus-starved microbes in the upper, aerobic ocean catabolize it for its phosphorus using EC 4.7.1.1, α-D-ribose 1-methylphosphonate 5-phosphate C-P-lyase. Since that enzyme releases methane, vast sections of the aerobic ocean are supersaturated with methane.

• alanine racemization
• flavin-N5-oxide biosynthesis
• methylphosphonate biosynthesis
• sodorifen biosynthesis

New Pathway from EcoCyc

• D-gulosides conversion to D-glucosides

New Pathways from Plant Metabolic Network (PMN)

We welcome two new curators at PMN, Angela Xu and Charles Hawkins, who contributed the following plant pathways.

A new pathway describes the biosynthesis of hydroxynitrile compounds that are produced by barley from L-leucine. One of these compounds, epiheterodendrin, is cyanogenic, releasing toxic hydrogen cyanide upon ingestion. The benzoxazinoids were identified in the early 1960s as secondary metabolites of the grasses (including the major agricultural crops maize, wheat, and rye) that function as natural pesticides and exhibit allelopathic properties. We extended our collection of benzoxazinoids pathways with a new pathway that describes two new methyltransferases and an oxygenase involved in their production. Other new pathways describe the biosynthesis of daurichromenate, a medically important compound known for its anti-HIV characteristics; the methylated cyclic sugar alcohol (cyclitol) L-quebrachitol, which plays a role in osmoregulation and osmoprotection; the ionotropic glutamate receptor agonist kainate, which is produced by red algae; and the iridoid compounds nepetalactones, which repel insects, but are also responsible for the psychoactive effects that plants belonging to the Nepeta genus (such as catnip) have on cats.

We also added pathways for the biosynthesis of several toxins. Domoic acid, which is produced by cyanobacteria of the genus Pseudo-nitzschia, is a neurotoxin affecting mammals. Ginkgotoxin, which is found in the seeds of the Ginkgo biloba plant, is known to cause seizures, paralysis, and sometimes death when ingested at a high dose. N-3-oxalyl-L-2,3-diaminopropanoate is a non-proteinogenic amino acid found in grass pea (Lathyrus sativus), a major source of protein for regions in South Asia and Sub-Saharan Africa. When consumed in large quantity it may lead to neurolathyrism, a paralysis of the lower limbs.

• 8-O-methylated benzoxazinoid glucoside biosynthesis
• daurichromenate biosynthesis
• domoic acid biosynthesis
• ginkgotoxin biosynthesis
• kainic acid biosynthesis
• leucine-derived hydroxynitrile glucoside biosynthesis
• N-3-oxalyl-L-2,3-diaminopropanoate biosynthesis
• nepetalactone biosynthesis
• quebrachitol biosynthesis

Other Revised Pathways

• 2,4,6-trichlorophenol degradation
• 3,5,6-trichloro-2-pyridinol degradation
• dibenzothiophene desulfurization
• pinitol biosynthesis I
• sulfide oxidation III (to sulfite)
• toluene degradation to 2-hydroxypentadienoate (via 4-methylcatechol)
• uracil degradation III

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of August 2019) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6349 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 23.0

MetaCyc KB Statistics

Pathways	2722
Reactions	15767
Enzymes	12267
Chemical Compounds	15655
Organisms	3009
Citations	60067
EC numbers	6280
Textbook Page Equivalency	9725

Released on Apr 29, 2019

New and Updated Pathways

We have added 23_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 12 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 35 new and updated pathways. We also revised two superpathways.

New Pathways

Ansamycin antibiotics biosynthesis: The ansamycins are a class of bacterial secondary metabolites that includes several important antibiotics such as the streptovaricins and rifamycins. They are named ansamycins (from the Latin ansa, handle) because of their unique structure, which consists of an aromatic moiety bridged at nonadjacent positions by an aliphatic chain. The different members of the ansamycin family differ mainly in their aromatic moiety, which can include a naphthalene ring, a naphthoquinone ring, a benzene ring or or a benzoquinone ring. We have revised significantly the existing pathway that describes the biosynthesis of rifamycin B, and added new pathways for ansatrienin, chaxamycin, mitomycin, naphthomycin, saliniketal A, and streptovaricin. We also added a pathway that describes the biosynthesis of cyclohexane-1-carboxyl-CoA, which serves as one of the building blocks of the ansatrienins. In addition, we have revised the pathway for the biosynthesis of 3-amino-5-hydroxybenzoate, which serves as the starter unit for the polyketide synthases involved in the biosynthesis of ansamycin and mitomycin class antibiotics.

• ansatrienin biosynthesis
• chaxamycin biosynthesis
• mitomycin biosynthesis
• naphthomycin biosynthesis
• saliniketal A biosynthesis
• streptovaricin biosynthesis
• cyclohexane-1-carboxyl-CoA biosynthesis

Nitrophenyl-containing compounds: The biosynthesis of compounds that contain a nitrophenyl moiety usually involves the 6-electron oxidation of an amino group attached to a benzene ring. The enzymes catalyzing this oxidation are unique and received much interest. We have added pathways that describe the biosynthesis of three such compounds: the antibiotic chloramphenicol; aureothin, which exhibits antifungal, insecticidal, antitumor, and anti-Helicobacter pylori activity; and spectinabilin, a compound related to aureothin that has shown activity against Rauscher Leukemia Virus (RLV) reverse transcriptase.

• aureothin biosynthesis
• chloramphenicol biosynthesis
• spectinabilin biosynthesis

Cytotoxins: We have added pathways describing the biosynthesis of three cytotoxic compounds. Cylindrospermopsin is a cytotoxin produced by some cyanobacteria. It has hepatotoxic, cytotoxic and neurotoxic effects, is a potential carcinogen, and has been involved in mass poisoning events. The bryostatins are a family of structurally related macrolide compounds originally found in the bryozoan Bugula neritina, a marine colonial filter-feeder. They are produced by bacterial endosymbionts of the bryozoans. Most of the bryostatins pharmacological effects are attributed to their interaction with the diacylglycerol binding site of a regulatory domain of EC 2.7.11.13, protein kinase C. In addition, bryostatins can function as very potent immunostimulants. Bryostatins are active against cancer cells and have been used in many clinical trials, both against cancer and against Alzheimer's disease. The third compound, pederin, is produced by bacterial endosymbionts of beetles from the Paederus and Paederidus genera. Pederin is one of the most potent non-proteinaceous substances ever isolated. When injected intravenously, it is more potent than the cobra venom.

• bryostatin biosynthesis
• cylindrospermopsin biosynthesis
• pederin biosynthesis

Plant metabolism: Two new plant pathways describe alkaloids produced by Coptis species. One pathway describes the biosynthesis of coptisine, an isoquinoline alkaloid that was originally isolated from rhizome of Coptis japonica. Coptisine has extensive pharmacological actions including antibacterial, hypoglycemic, anti-tumorigenic, and gastric-mucous membrane protection. In addition, coptisine was reported to exert antidepressant effects as a potent type A monoamine oxidase inhibitor. The second pathway describes the biosynthesis of epiberberine, which has broad biological activity, including antihyperlipidemic and antihyperglycemic effects, as well as anti-inflammatory, anti-Alzheimer and antioxidant effects. It is also a potent urease inhibitor and is known to interact with human organic cation transporters and cytochrome P-450 enzymes. We have also significantly revised the plant cholesterol biosynthetic pathway, which is now complete.

• coptisine biosynthesis
• epiberberine biosynthesis

Mammalian metabolism: A new pathway describes the biosynthesis of ophthalmate, a tripeptide analog of glutathione in which L-cysteine is replaced by (S)-2-aminobutanoate. It was first discovered during the study of peptides present in calf lens, and was named based on its presence in that tissue. Serum ophthalmate concentration has been suggested as a sensitive indicator of hepatic glutathione depletion.

Endocanabinoids: The endobanabinoids are the endogenous agonists of the canabinoid receptors CB1 and CB2. Through their associated Gi/o proteins, activation of the cannabinoid receptors results in a decrease in the intracellular level of cAMP, activation of EC 2.7.11.24, mitogen-activated protein kinase, and modulation of ion channels, leading to the activation of A-type and inward-rectifier potassium channels and the inhibition of N-type and P/Q-type calcium channels. Five compounds are known to function as endocanabinoids - anandamide (N-arachidonoyl ethanolamide), 2-arachidonoylglycerol, 2-arachidonoyl glyceryl ether, virodhamine (O-arachidonoyl ethanolamine), and N-arachidonoyl-dopamine. We have added two pathways for the biosynthesis of anandamide and one pathway for the biosynthesis of 2-arachidonoylglycerol. We also added a pathway that describes the lipoxygenation of anandamide.

• 2-arachidonoylglycerol biosynthesis
• anandamide biosynthesis I
• anandamide biosynthesis II
• anandamide lipoxygenation

Lipid metabolism: The endocanabinoid anandamide belongs to the N-acylethanolamines, a class of endogenous bioactive lipid molecules formed by the linkage of an acyl group to the nitrogen atom of ethanolamine. We have added a biosynthetic pathway for another member of this class, palmitoyl ethanolamide. Work by the Nobel laureate Rita Levi-Montalcini has shown that palmitoyl ethanolamide is a natural modulator of hyperactive mast cells, counteracting the pro-inflammatory actions of the Nerve Growth Factor (NGF). It has been effective in a number of animal models for inflammation, neuroinflammation, neurotoxicity, and chronic pain.

Two other pathways describe the biosynthesis of acylceramides -- epidermis-specific ceramide species that are very important for skin barrier formation. Acylceramides consist of a ceramide ester linked to linoleate. The chain-length of the fatty acid within the ceramide moiety is extremely long (C28–C36), making acylceramides some of the most hydrophobic lipids in mammalian bodies. One of the pathways describes the formation of these ultra-long-chain fatty acids, while the other describes the formation of the acylceramides.

• palmitoyl ethanolamide biosynthesis
• acylceramide biosynthesis
• ultra-long-chain fatty acid biosynthesis

Revised Pathways

• (9Z)-tricosene biosynthesis
• 15-epi-lipoxin biosynthesis
• 3-amino-5-hydroxybenzoate biosynthesis
• artemisinin and arteannuin B biosynthesis
• aspirin triggered resolvin E biosynthesis
• cholesterol biosynthesis (plants)
• indole-3-acetate degradation
• lipoxin biosynthesis
• rifamycin B biosynthesis
• sphingolipid biosynthesis (yeast)
• ubiquinol-6 biosynthesis from 4-aminobenzoate (yeast)
• very long chain fatty acid biosynthesis II

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of March 2019) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6280 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 22.6

MetaCyc KB Statistics

Pathways	2698
Reactions	15413
Enzymes	12111
Chemical Compounds	15263
Organisms	2980
Citations	58954
EC numbers	6201
Textbook Page Equivalency	9517

Released on Dec 12 2018

New and Updated Pathways

We have added 30_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 7 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 37 new and updated pathways. Of the new pathways, 18 were contributed by Hartmut Foerster of the Boyce Thompson Institute, 3 were contributed by EcoCyc curators, and one was imported from the PGDB for Salmonella enterica enterica 14028S. We also added five new superpathways, all submited by H. Foerster.

New Pathways

Sterol biosynthesis: Sterols such as ergosterol, sitosterol and cholesterol are isoprenoid-derived molecules that have essential functions in eukaryotes. Some bacterial species also produce sterols, although the function of sterols in these organisms is still not well understood. We added a new pathway describing sterol biosynthesis by a group of aerobic methylotrophs. We also added pathways describing the biosynthesis of cycloartenol, a precursor for all the steroids produced by plants, and of parkeol, a rare isomer of lanosterol that is produced by plants and some bacteria.

• cycloartenol biosynthesis
• parkeol biosynthesis
• sterol biosynthesis (methylotrophs)

Bacterial protein modification: The formation of disulfide bonds is crucial for the folding and stability of many membrane and secreted proteins. The decrease in chain entropy that accompanies disulfide bond formation disfavors the unfolded form and helps stabilize the tertiary structure of the protein. We added a new pathway that describes the DsbAB system, which operates in the periplasmic space of Gram-negative bacteria to introduce disulfide bonds. We also added a pathway that describes how electrons from thioredoxin are used to reduce disulfide bonds.

• periplasmic disulfide bond formation
• periplasmic disulfide bond reduction

Biosynthetic pathways: A new pathway describes the biosynthesis of prenylated flavin mononucleotide, a cofactor required by the UbiD family of reversible decarboxylases involved in ubiquinone biosynthesis, biological decomposition of lignin, and biotransformation of aromatic compounds. Another new biosynthetic pathway describes the biosynthesis of salmochelins, C-glucosylated siderophores related to enterobactin that are produced by Salmonella species, uropathogenic and avian pathogenic Escherichia coli strains, and certain Klebsiella strains. We also added a pathway describing salmochelins degradation.

• prenylated FMNH₂ biosynthesis
• salmochelin biosynthesis
• salmochelin degradation

Other degradation pathways: A new degradation pathway describes the aerobic degradation of cyanuric acid, a common intermediate in the degradation of hundreds of s-triazine compounds, including herbicides, dyes, and resin intermediates such as melamine. A second pathway describes the degradation of fructosyllysine and glucosyllysine by Salmonella enterica enterica. These compounds are generated non-enzymatically by condensation of sugars with the amino acid, followed by a spontaneous rearrangement. Another new pathway describes the anaerobic degradation of limonene by Castellaniella defragrans. Revised pathways (see below) include the anaerobic degradation of benzoyl-CoA and cyclohexane-1-carboxylate, and a second pathway for cyanuric acid degradation.

• cyanuric acid degradation I
• fructoselysine and glucoselysine degradation
• limonene degradation (anaerobic)

Plant metabolism:

New plant pathways describe the biosynthesis of glycoalkaloids, diterpenoids, phenylpropanoids, and volatile organic compounds (VOCs).
Acylsugars, which contain one, two, three or four acyl moieties, appear to be restricted to the Solanaceae family. They are secreted by specialized epidermal organs called trichomes to the surface area of the plants, where they constitute the first physical barrier against herbivores. Although the acylsugars formed by different Solanaceae species are generally comparable, their biosynthetic pathways may differ considerably among different species.

A number of compounds are produced in the glandular trichomes of the Solanaceae family besides acylsugars. Many of those are diterpenoids that can be classified into two groups - the macrocyclic cembrenoids (such as α-cembratriene-4,6-diol) and the dicyclic labdanoids (labdenediol and sclareol). The biosynthetic pathways of those compounds have been added to MetaCyc, along with that of the labdanoid cis-abienol, which appears to exhibit a special role in protecting Nicotiana species from pathogens.

The glycoconjugate gentisate 5-O-β-xylopyranoside is involved in systemic, non-necrotizing infections of tomato plants, and is crucial for the defense against viroid infections. A new pathway describes its formation from gentisate.

Several new pathways describe the formation of compounds that define taste, aroma and color in valuable fruits of solanaceous plants. Methylsalicylate and guaiacol are volatile organic compounds (VOCs) known to play an important role in defining taste and aroma in fruits such as tomato. Both compounds form glycoconjugates (e.g. guaiacol O-β-D-xylopyranosyl-(1→6)-O-β-D-glucopyranoside), and the conversion of the free compound to the glycoconjugate is an important process in aroma determination.

Another new pathway describes the biosynthesis of indole-3-carbonyl nitrile, a novel secondary metabolite observed in Arabidopsis thaliana. The compound contains a highly reactive α-ketonitrile moiety that has not been found in any plant natural product previously. The α-ketonitrile is susceptible to nucleophilic attack, leading to the displacement of a cyanide ion, a common defense mechanism in cyanogenic plants.

In addition, several important plant secondary metabolite pathways have been revised. Several missing and uncharacterized steps in the pathway leading to the anti-arrhythmic drug ajmaline have been updated. Similarly, the pathway leading to the important chemotherapy agents vindoline, vindorosine and vinblastine has been significanty revised.

• 4-hydroxyindole-3-carbonyl nitrile biosynthesis
• α-tomatine biosynthesis
• α-tomatine degradation
• cis-abienol biosynthesis
• acylsucrose biosynthesis (Solanum habrochaites)
• acylsucrose biosynthesis (Solanum pennellii)
• cembratrienediol biosynthesis
• diacylsucrose biosynthesis (Solanum)
• gentisate 5-O-β-D-xylopyranoside biosynthesis
• guaiacol biosynthesis
• labdenediol and sclareol biosynthesis
• methylsalicylate biosynthesis
• methylsalicylate degradation
• monoacylsucrose biosynthesis (Solanum)
• phenylpropanoid volatiles glycoconjugation (tomato)
• solasodine biosynthesis
• solasodine glycosylation
• tetraacylsucrose biosynthesis (Solanum)
• triacylsucrose biosynthesis (Solanum)

New Superpathways

• superpathway of acylsucrose biosynthesis (cultivated tomato)
• superpathway of acylsucrose biosynthesis (wild tomato)
• superpathway of glandular trichomes produced diterpenoids (tobacco)
• superpathway of glycoalkaloid metabolism (Solanaceae)
• superpathway of methylsalicylate metabolism

Revised Pathways

• ajmaline and sarpagine biosynthesis
• benzoyl-CoA degradation III (anaerobic)
• cyanuric acid degradation II
• cyclohexane-1-carboxylate degradation (anaerobic)
• glutaminyl-tRNA^gln biosynthesis via transamidation
• L-asparagine biosynthesis III (tRNA-dependent)
• vindoline, vindorosine and vinblastine biosynthesis

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of November 2018) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6201 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 22.5

MetaCyc KB Statistics

Pathways	2666
Reactions	15198
Enzymes	12006
Chemical Compounds	15090
Organisms	2960
Citations	58066
EC numbers	6134
Textbook Page Equivalency	9372

Released on Sep 25 2018

New and Updated Pathways

We have added 26_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 19 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 45 new and updated pathways. We also revised 3 superpathways.

New Pathways

Amino acid biosynthesis: We added several new variants of amino acid biosynthetic pathways. Two pathways describe the formation of L-cysteine from 3-phospho-L-serine. One of those was described from hyperthermophilic archaea, while the other is found in the protozoan parasite Trichomonas vaginalis. The third is a plant pathway that operates in the cytosol and produces L-serine via (R)-glycerate.

• L-cysteine biosynthesis VIII (Thermococcus kodakarensis)
• L-cysteine biosynthesis IX (Trichomonas vaginalis)
• L-serine biosynthesis II

Amino acid degradation: The bacterium Acetoanaerobium sticklandii and some other Clostridial species can utilize combinations of amino acids for growth using Stickland reactions. Stickland reactions, named after their discoverer, L. H. Stickland, are fermentations of amino acid pairs in which one amino acid is oxidized and the other is reduced. The oxidation branch of the Stickland reaction leads to formation of ATP by substrate-level phosphorylation, but produces reducing equivalents, which are consumed during the reduction of other amino acids via the reducing branch, maintaining a balanced redox potential in the cell. During this period we added 4 new pathways that describe this form of amino acid fermentation.

• glycine degradation (Stickland reaction)
• L-phenylalanine degradation VI (Stickland reaction)
• L-tryptophan degradation XIII (Stickland reaction)
• L-tyrosine degradation V (Stickland reaction)

Other degradation pathways: New degradation pathways describe the aerobic degradation of 4-coumarate and trans-caffeate by some bacterial species. A new old pathway describes the oxidative degradation of D-xylose, known as the Weimberg pathway after R. Weimberg who proposed it back in 1961. In addition, the existing androstenedione degradation pathway, the later part of which has been previously uncharacterized, was updated with recent information and is now complete.

• 4-coumarate degradation (aerobic)
• androstenedione degradation
• D-xylose degradation V
• trans-caffeate degradation (aerobic)

Secondary metabolite biosynthesis: Itaconate is an unsaturated acid with conjugated double bonds and two carboxyl groups. It was discovered in 1837 and named as an anagram of cis-aconitate. Itaconate inhibits EC 4.1.3.1, isocitrate lyase, the key enzyme of the glyoxylate shunt, which is essential for bacterial growth under specific conditions. Its production by mammalian macrophages can inhibit the growth of pathogenic bacteria and is considered an immune defense. We have revised the existing pathway of itaconate biosynthesis and  added a second variant. In addition, we added a pathway used by some fungi to convert itaconate to the tricarboxylate itatartarate.
The antibiotic mupirocin, which is produced by Pseudomonas fluorescens NCIMB 10586, is a mixture of four pseudomonic acids. It is used as a topical treatment for bacterial skin infections such as impetigo or folliculitis, and is also used to treat nose infections of methicillin resistant Staphylococcus aureus (MRSA). The full pathway is now available.
Staphyloferrin B is one of four siderophores produced by Staphylococcus aureus. Siderophores are compounds with a very high affinity for iron, which are secreted by bacteria into the medium, where they complex the iron, and then transported back into the cell. Another Staphylococcus aureus pathway described the production of staphylopine, metallophore that is involved in the acquisition of nickel, copper, and cobalt.

• 2-hydroxyparaconate and itatartarate biosynthesis
• itaconate biosynthesis II
• mupirocin biosynthesis
• staphyloferrin B biosynthesis
• staphylopine biosynthesis

Salvage pathways: In yeast, sirtuins regulate gene silencing by histone deacetylation via formation of 2''-O-acetyl-ADP-ribose. The byproduct of this reaction is nicotinamide, which is salvaged back to NAD⁺ by this new pathway.

• NAD salvage pathway V (PNC V cycle)

Archaeal metabolism: We added a pathway used by some archaeons that belong to the Crenarchaeota phylum for the synthesis of UDP-N-acetyl-α-D-galactosamine, the ubiquitous amino sugar nucleotide donor of N-acetyl-D-galactosamine (GalNAc) residues for the biosynthesis of cell surface structures. We also revised the archaeal variant of the mevalonate pathway.

• UDP-N-acetyl-D-galactosamine biosynthesis III
• mevalonate pathway III (archaea)

Plant metabolism: A new pathway describes the biosynthesis of dolabralexins, a group of diterpenoids produced by maize that are active against fungal pathogens such as Fusarium verticillioides and Fusarium graminearum. Another new pathway describes the biosynthesis of 3-methyl-3-sulfanylbutan-1-ol, one of the main aroma components in passion fruit juice. Interestingly, it is also the key odoriferous component of cat urine.

Tricin is a flavonoid typically distributed in sedges, palms, and grasses, including cereal crops such as rice, wheat, barley, maize, and sorghum. It is considered a major candidate to be developed as a nutraceutical because of its antioxidant, anticancer, anti-inflammatory, and cardiovascular-protective properties.

A major revision of the noscapine biosynthetic pathway resulted in the filling of all previously unknown steps. Other significantly revised plant pathways include ginsenosides biosynthesis, marneral biosynthesis, secologanin and strictosidine biosynthesis, a variant of (3E)-4,8-dimethylnona-1,3,7-triene biosynthesis characterized from Arabidopsis thaliana, and tricetin methylation.

• (3E)-4,8-dimethylnona-1,3,7-triene biosynthesis II
• dolabralexins biosynthesis
• felinine and 3-methyl-3-sulfanylbutan-1-ol biosynthesis
• ginsenosides biosynthesis
• marneral biosynthesis
• noscapine biosynthesis
• tricin biosynthesis
• secologanin and strictosidine biosynthesis
• tricetin methylation

Vitamin K metabolism: Vitamin K-dependent proteins are modified in metazoans by carboxylation of clusters of glutamate residues to carboxylated glutamate as they transit through the endoplasmic reticulum. The carboxylation is catalyzed by EC 4.1.1.90, peptidyl-glutamate 4-carboxylase, an enzyme that uses various vitamin-K hydroquinones, including menaquinol, as co-substrates that are epoxidated during the reaction, generating vitamin K 2,3-epoxide. This posttranslational protein modification is the only firmly established biochemical function of vitamin K in metazoa. We added two pathways related to the metabolim of vitamin K. One pathway describes a metazoan variant for the biosynthesis of menaquinol-4, while the other describes the recycling of the epoxide back to the phylloquinol active form. Other related new pathways describe the non-metazoan route of demethylmenaquinol-4 and menaquinol-4 biosynthesis.

• demethylmenaquinol-4 biosynthesis
• menaquinol-4 biosynthesis I
• menaquinol-4 biosynthesis II
• vitamin K degradation
• vitamin K-epoxide cycle

Glycan pathways: We added a new pathway that describes the degradation of the plant polymer arabinogalactan type II (AG type II). This polymer, also known as arabino-3,6-galactan, has a (1→3)-β-D-Galp backbone heavily substituted at position 6 by mono- and oligosaccharide side chains composed of arabinosyl and galactosyl units. It occurs in cell walls of dicots and cereals, often linked to proteins (known as arabinogalactan proteins). In addition we have revised our existing pathways for the degradation of the plant polymers rhamnogalacturonan type I, glucuronoarabinoxylan, and homogalacturonan, as well as the biosynthesis of the Escherichia coli lipid A-core lipopolysaccharide, to use glyco-CT displays.

• glucuronoarabinoxylan degradation
• homogalacturonan degradation
• lipid A-core biosynthesis (E. coli K-12)
• plant arabinogalactan type II degradation
• rhamnogalacturonan type I degradation I

Other Revised Pathways

• 4-hydroxybenzoate biosynthesis I (eukaryotes)
• camptothecin biosynthesis
• D-xylose degradation III
• fosfomycin biosynthesis
• itaconate biosynthesis I
• (S)-propane-1,2-diol degradation
• (S)-reticuline biosynthesis II

Revised Superpathways

• superpathway of cholesterol degradation I (cholesterol oxidase)
• superpathway of cholesterol degradation II (cholesterol dehydrogenase)
• superpathway of testosterone and androsterone degradation

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of August 2018) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6134 EC numbers (including internal M numbers).

Three important changes took place in the EC system during this release. One is the introduction of a new upper class (EC 7) for translocases - enzymes that catalyze the movement of ions or molecules across membranes or their separation within membranes (e.g. ATP-type transporters). The second is the introduction of subclass EC 5.6 for macromolecular conformational isomerases - enzymes that catalyze changes to the conformations of macromolecules (e.g. DNA helicases). The third change is the reclassification of many cytochrome P-450 enzymes under the EC 1.14.14 and EC 1.14.19 sub-subclasses. Many of those enzymes were previously classified incorrectly under the EC 1.14.13 sub-subclass.

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Release Notes for MetaCyc Version 22.0

MetaCyc KB Statistics

Pathways	2642
Reactions	14971
Enzymes	11848
Chemical Compounds	14847
Organisms	2941
Citations	56914
EC numbers	6093
Textbook Page Equivalency	9194

Released on Apr 24, 2018

New and Updated Pathways

We have added 41_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 43 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 84 new and updated pathways. We also added one new superpathway.

New Pathways

Cobamide biosynthesis: The cobamides are complex cobalt-containing cofactors that are required for the enzymatic activity of many enzymes. Four of the six coordination sites of the cobalt ion are provided by the corrin ring, while the other two are provided by upper (Coβ) and lower (Coα) ligands. Most readers are likely familiar with adenosylcobalamin, the cofactor used by eukaryotic organisms in which the two ligands are 5'-deoxyadenosyl and 5,6-dimethylbenzimidazole, respectively. However, most bacteria utilize different forms of cobamides in which the upper ligand is often a methyl group while the lower ligand is one of 16 different compounds. We have added a large number of pathways that describe the biosynthesis of these bacterial cobamides, rearranged our current cobamide biosynthesis pathways, and added a few new cobamide salvage pathways.

• 2-methyladeninyl adenosylcobamide biosynthesis from adenosylcobinamide-GDP
• 4-methylphenyl adenosylcobamide biosynthesis from adenosylcobinamide-GDP
• 5-hydroxybenzimidazolyl adenosylcobamide biosynthesis from adenosylcobinamide-GDP
• 5-methoxy-6-methylbenzimidazolyl adenosylcobamide biosynthesis from adenosylcobinamide-GDP
• 5-methoxybenzimidazolyl adenosylcobamide biosynthesis from adenosylcobinamide-GDP
• 5-methylbenzimidazolyl adenosylcobamide biosynthesis from adenosylcobinamide-GDP
• adeninyl adenosylcobamide biosynthesis from adenosylcobinamide-GDP
• adenosylcobalamin biosynthesis from adenosylcobinamide-GDP II
• adenosylcobinamide-GDP biosynthesis from cobyrinate a,c-diamide
• adenosylcobinamide-GDP salvage from cobinamide I
• adenosylcobinamideGDP salvage from cobinamide II
• benzimidazolyl adenosylcobamide biosynthesis from adenosylcobinamide-GDP
• cobalamin salvage (eukaryotic)
• phenyl adenosylcobamide biosynthesis from adenosylcobinamide-GDP

Siderophore biosynthesis: Iron is an essential trace element. In the presence of oxygen, ferrous iron is rapidly oxidized to ferric iron, which tends to form insoluble compounds and becomes unavailable to organisms. As a result, the level of physiologically available iron can drop far below 1 μM and become growth-limiting for bacteria. To survive, many bacteria evolved specialized transport systems called siderophores, which are low molecular mass compounds that complex and retract iron ions.
We have added several new siderophore biosynthesis pathways (and revised an existing one), bringing the total of siderophore biosynthetic pathways in MetaCyc to 26.

• acinetobactin biosynthesis
• acinetoferrin biosynthesis
• anguibactin biosynthesis
• baumannoferrin biosynthesis
• pseudomonine biosynthesis
• pyochelin biosynthesis
• staphyloferrin A biosynthesis
• vanchrobactin biosynthesis

Archaeal pathways: We added two new pathways found in archaea. One pathway describes methionine biosynthesis utilizing hydrogen sulfide as the sulfur source. The other pathway described sulfur reduction in the thermophile Pyrococcus furiosus.

• L-methionine biosynthesis IV (archaea)
• sulfur reduction III

Isonitrile compounds biosynthesis: Isonitrile-functionalized compounds are not very common, though analyses of metagenomic sequences suggest that the enzymes that produce them are much more prevalent than previously thought. We added pathways describing the biosynthesis of three such compounds. The first compound, 3-[(E)-2-isocyanoethenyl]-1H-indole, has antibacterial activity against Gram-positive bacteria. Paerucumarin is an iron-chelating compound whose function is not yet known, while rhabduscin, a potent inhibitor of insect tyrosinase (EC 1.14.18.1), is produced by bacterial symbionts of nematodes that infect insect larvae, and is used as a chemical weapon by the nematodes.

• 3-[(E)-2-isocyanoethenyl]-1H-indole biosynthesis
• paerucumarin biosynthesis
• rhabduscin biosynthesis

Hapalindole-type alkaloids biosynthesis: Hapalindole-type alkaloids are a group of hybrid isoprenoid-indole alkaloids produced solely by members of Subsection V of the cyanobacteria, such as the Fischerella and Hapalosiphon genera. These compounds often have antibacterial, antimycotic, or antialgal activities.

• 12-epi-hapalindole biosynthesis
• fischerindole biosynthesis
• hapalindole biosynthesis

Protein glycosylation pathways: We added two new protein glycosylation pathways. One pathway describes the formation of the core M3 glycan on mammalian proteins, and the other describes the extension of core M3 to the complex glycan found on the α-dystroglycan protein.

• α-dystroglycan glycosylation
• protein O-mannosylation III (mammals, core M3)

Electron transfer pathways: We added two new bacterial anaerobic electron transfer pathways that utilize hydrogen peroxide as the electron acceptor via the activity of cytochrome c peroxidase (ccp).

• glycerol-3-phosphate to hydrogen peroxide electron transport
• NADH to hydrogen peroxide electron transfer

Other New Biosynthetic Pathways

• ATP biosynthesis
• β-dihydromenaquinone-9 biosynthesis
• tabtoxinine-β-lactam biosynthesis
• toxoflavin biosynthesis
• UDP-N-acetylmuramoyl-pentapeptide biosynthesis III (meso-diaminopimelate containing)

Other New Degradation Pathways

• N-methylpyrrolidone degradation
• oxalate degradation VI
• pinoresinol degradation

New Superpathways

• superpathway of menaquinol-8 biosynthesis III

Revised Pathways

Glycan pathways: Due to the size and complexity of complex glycans, pathways describing their biosynthesis and degradation are difficult to follow when using the full molecular detail of the molecules involved. The use of GlycoCT icons makes such diagrams much easier to follow. During this release we have updated many of our existing glycan pathways to use GylcoCT icons (Ceroni et al,Source Code Biol Med. 2007 Aug 7;2:3).

• β-D-galactosaminyl-(1→3)-N-acetyl-α-D-galactosamine biosynthesis
• (1,3)-β-D-xylan degradation
• (1,4)-β-D-xylan degradation
• Escherichia coli serotype O86 O-antigen biosynthesis
• Escherichia coli serotype O9a O-antigen biosynthesis
• ABH and Lewis epitopes biosynthesis from type 1 precursor disaccharide
• ABH and Lewis epitopes biosynthesis from type 2 precursor disaccharide
• acetan biosynthesis
• biosynthesis of Lewis epitopes (H. pylori)
• complex N-linked glycan biosynthesis (plants)
• complex N-linked glycan biosynthesis (vertebrates)
• fructan biosynthesis
• glycosaminoglycan-protein linkage region biosynthesis
• heparan sulfate biosynthesis
• i antigen and I antigen biosynthesis
• mucin core 1 and core 2 O-glycosylation
• mucin core 3 and core 4 O-glycosylation
• protein N-glycosylation (Haloferax volcanii)
• protein N-glycosylation initial phase (eukaryotic)
• protein N-glycosylation processing phase (plants and animals)
• protein O-mannosylation I (yeast)
• protein O-mannosylation II (mammals, core M1 and core M2)
• terminal O-glycans residues modification (via type 2 precursor disaccharide)
• xyloglucan biosynthesis

Glutathione-mediated detoxification: We have revised two existing pathway variants that describe a common route for detoxification and processing of xenobiotics, found in fungi, plants, and animals. The xenobiotics are conjugated to glutathione, followed by sequestration and degradation.

• glutathione-mediated detoxification I
• glutathione-mediated detoxification II

Other revised biosynthetic pathways

• (2S,3E)-2-amino-4-methoxy-but-3-enoate biosynthesis
• ω-sulfo-II-dihydromenaquinone-9 biosynthesis
• formaldehyde assimilation I (serine pathway)
• justicidin B biosynthesis
• L-isoleucine biosynthesis V
• L-phenylalanine biosynthesis III (cytosolic, plants)
• PRPP biosynthesis

Other revised degradation pathways

• 2-hydroxypenta-2,4-dienoate degradation
• 3,4,6-trichlorocatechol degradation
• 4,5-dichlorocatechol degradation
• ethanolamine utilization
• heme degradation I
• L-threitol degradation
• nylon-6 oligomer degradation
• toluene degradation to 2-hydroxypentadienoate (via 4-methylcatechol)

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of March 2018) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6093 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 21.5

MetaCyc KB Statistics

Pathways	2609
Reactions	14654
Enzymes	11680
Chemical Compounds	14411
Organisms	2914
Citations	55666
EC numbers	6044
Textbook Page Equivalency	8968

Released on Nov 28, 2017

New and Updated Pathways

We have added 37_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 8 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 46 new and updated pathways. We also added one new superpathway.

New Pathways of General Applicability

N-linked glycosylation is an important protein post-translational modification in eukaryotes and archaea, and very rarely, in bacteria. During this process certain oligosaccharides are attached to an L-asparagine residue in the polypeptide chain of target proteins. The composition and structure of the oligosaccharide varies greatly among kingdoms and to a lesser degree among species. N-linked glycosylation in eukaryotes consists of three stages: the initial synthesis of a high-mannose, dolichol phosphate-linked precursor tetradecasaccharide and its transfer from the dolichol phosphate anchor to a newly synthesized polypeptide; the trimming (processing) of these high-mannose structures by α-glucosidases and α-mannosidases, which occurs in the ER and Golgi complex; and the synthesis of complex branched oligosaccharide chains, carried out by Golgi glycosyltransferases. In the past MetaCyc only contained a pathway describing the first stage. We have now added pathways describing all stages of the process in multiple kingdoms, and revised an existing archaeal pathway. New and revised N-glycosylation pathways include:

• complex N-linked glycan biosynthesis (plants)
• complex N-linked glycan biosynthesis (vertebrates)
• protein N-glycosylation (Haloferax volcanii)
• protein N-glycosylation processing phase (yeast)
• protein N-glycosylation processing phase (plants and animals)

Carotenoid metabolism: Carotenoids are isoprenoid pigments in the yellow to red color range. They are commonly produced by photosynthetic organisms, but also by some non-photosynthetic fungi and bacteria. In photosynthetic organisms cartenoids participate in light harvesting and provide protection against photooxidative stress through energy-dissipation of excess light absorbed by the antenna pigments. In non-photosynthetic organisms carotenoids serve multiple roles, such as antioxidants, virulence factors, and modulators of membrane function. Animals, including humans, cannot synthesize carotenoids, but require them for the synthesis of retinoids and vitamin A. We have reorganized and updated our coverage of carotenoid biosynthesis by adding all known pathways as of September 2017. New pathways include:

• bacterioruberin biosynthesis
• C.p.450 monoglucoside biosynthesis
• chlorobactene biosynthesis
• diadinoxanthin and diatoxanthin interconversion
• diadinoxanthin and fucoxanthin biosynthesis
• flexixanthin biosynthesis
• isorenieratene biosynthesis I (actinobacteria)
• isorenieratene biosynthesis II (Chlorobiaceae)
• lauryl-hydroxychlorobactene glucoside biosynthesis
• lycopadiene biosynthesis
• sarcinaxanthin diglucoside biosynthesis

We also revised several existing carotenoid biosynthesis pathways including:

• β-carotene biosynthesis
• trans-lycopene biosynthesis I
• trans-lycopene biosynthesis II (oxygenic phototrophs and green sulfur bacteria)
• violaxanthin, antheraxanthin and zeaxanthin interconversion

Bioluminescence: throughout evolution, bioluminescence has been reinvented many times; some 30 different independent systems are still extant. We added two new pathways that describe bioluminescence in fungi and in the fire squid, bringing the total of MetaCyc bioluminescence pathways to seven.

• fungal bioluminescence
• squid bioluminescence

Brominated compounds biosynthesis: Marine organisms, including bacteria, algae and invertebrates, produce many brominated compounds. In some marine sponges within the Dysideidae family polybrominated diphenyl ethers can exceed 10% of the sponge tissue by dry weight. In many cases the origin of the compounds was shown to be symbiotic bacteria. We have added several new pathways that describe bacterial biosynthesis of organobromine compounds.

• brominated pyrroles biosynthesis
• polybrominated biphenyls and diphenyl ethers biosynthesis
• polybrominated dihydroxylated diphenyl ethers biosynthesis
• β-dihydromenaquinone-9 biosynthesis
• ATP biosynthesis
• sulfur reduction III
• L-methionine biosynthesis IV (archaea)
• tabtoxinine-β-lactam biosynthesis
• toxoflavin biosynthesis
• UDP-N-acetylmuramoyl-pentapeptide biosynthesis III (meso-diaminopimelate containing)
• toxoflavin biosynthesis
• UDP-N-acetylmuramoyl-pentapeptide biosynthesis III (meso-diaminopimelate containing)

Sulfur metabolism

A new pathways is a mammalian degradation pathway for carbon disulfide (CS₂), a gas that is widely used as an industrial solvent and as a fumigant in agriculture. Exposure to CS₂ has been associated with increased risk of cardiovascular disease, ischemic heart disease mortality, and adverse effects on the nervous system. A revised pathway describes all of the different sources for hydrogen sulfide production in mammalian cells, while another new pathway describes how the sulfide is oxidized to sulfate and thiosulfate. Another revised pathway describes the bacterial production of hydrogen sulfide from thiocyanate via carbonyl sulfide (COS).

• carbon disulfide oxidation III (metazoa)
• hydrogen sulfide biosynthesis II (mammalian)
• sulfide oxidation IV (metazoa)
• thiocyanate degradation II

5-Oxo-L-proline metabolism: 5-Oxo-L-proline, also known as L-pyroglutamate, is formed via the spontaneous cyclization of L-glutamine, L-glutamate, and related metabolites. Under physiological conditions L-glutamine cyclizes to 5-oxo-L-proline at the rate of 10% per day. Accumulation of the compound is deleterious and results in growth inhibition and interference with energy production, lipid synthesis, and antioxidant defenses. We added a new pathway that describes the formation and metabolism of 5-oxo-L-proline.

• 5-oxo-L-proline metabolism

Pathways of Microbial Metabolism

Levulinate degradation: 4-Oxopentanoate (commonly known as levulinate) is readily obtained from biomass through non-enzymatic acid hydrolysis of a wide range of feedstocks. It is considered important commercially, as it can be used as a renewable feedstock for the production of fuel additives, flavors, fragrances, and polymers. In addition, calcium levulinate is used as a common oral and parenteral source of calcium. We added a pathway describing both the formation and degradation of the compound.

• levulinate degradation

Nickel cofactor biosynthesis: Pyridinium-3-thioamide-5-thiocarboxylate mononucleotide Ni pincer complex, commonly known as a "nickel cofactor", is a unique cofactor produced by the bacterium Lactobacillus plantarum from nicotinate adenine dinucleotide, a precursor of NAD.

• nickel cofactor biosynthesis

Glutathione-mediated detoxification: These important pathways describe a detoxification mechanism in which glutathione (GSH) binds to electrophilic chemicals, forming conjugates that are exported from the cell. We have added two variants - one from mammals, the other from fungi and plants.

• glutathione-mediated detoxification I
• glutathione-mediated detoxification II

Psilocybin biosynthesis: Psilocybin is the major constituent in magic mushrooms, members of the Psilocybe genus that produce psychotropically active natural products. Upon ingestion, psilocybin is rapidly dephosphorylated to generate psilocin, the actual psychotropic agent.We added a pathway that describes the biosynthesis of these compounds from the amino acid L-tryptophan.

• psilocybin biosynthesis

Pyoluteorin biosynthesis: A new pathway describes the biosynthesis of pyoluteorin, a hybrid polyketide-nonribosomal peptide product that carries two chlorine atoms on a pyrrole moiety attached to a resorcinol ring. The compound, which is produced by some Pseudomonads, has antimicrobial and antifungal activities, and is particularly toxic against Oomycetes.

• pyoluteorin biosynthesis

Ellagic acid degradation: Urolithins are intestinal microbial metabolites produced from ellagitannin- and ellagic acid-containing foods such as walnuts, strawberries, and pomegranates. The urolithins are absorbed much better than their precursors, and thus contribute significantly to the beneficial properties attributed to those foods. They possess anti-inflammatory, anticarcinogenic, antiglycative, antioxidant, and antimicrobial effects. Although no enzymes associated with their formation have been characterized, a pathway has been described.

• ellagic acid degradation to urolithins

Other Pathways of Microbial Metabolism

• archaeosine biosynthesis II
• glycerol-3-phosphate to hydrogen peroxide electron transport
• NADH to hydrogen peroxide electron transfer
• rubber degradation I
• rubber degradation II

Pathways of Eukaryotic Metabolism

O-linked protein mannosylation: We also created two new pathways that describe the process of protein O-mannosylation, which is an essential protein modification in fungi and animals.

• protein O-mannosylation I (yeast)
• protein O-mannosylation II (mammals)

Melanin biosynthesis: Pheomelanin is a common type of melanin pigment, which is found in hair and skin of mammals. Pheomelanin imparts a pink to red hue and is accordingly found in large quantities in red hair. In skin pheomelanin is particularly concentrated in the lips, nipples, glans of the penis, and vagina. A pathway describing pheomelanin biosynthesis has been added, complementing the existing pathways that describe L-dopachrome and eumelanin biosynthesis.

• pheomelanin biosynthesis

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of September 2017) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 6044 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 21.1

MetaCyc KB Statistics

Pathways	2572
Reactions	14347
Enzymes	11547
Chemical Compounds	14003
Organisms	2883
Citations	54196
EC numbers	5959
Textbook Page Equivalency	8777

Released on August 15, 2017

New and Updated Pathways

We have added 45_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 13 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 58 new and updated pathways. We also added commentary to 11 existing superpathways.

New Pathways of General Applicability

Throughout evolution, bioluminescence has been reinvented many times; some 30 different independent systems are still extant. About two years ago we introduced a pathway describing bacterial bioluminescence. We now expanded our coverage to describe bioluminescence in jellyfish, corals, dinoflagellates and fireflies.

• jellyfish bioluminescence
• coral bioluminescence
• dinoflagellate bioluminescence
• firefly bioluminescence

The uridine³⁴ wobble bases of tRNA^Gln, tRNA^Lys and tRNA^Glu are universally modified, although different modifications occur in different taxa and even in different cell compartments. We added pathways that describe the differenellagic acid degradation ott types of 2-thiolation modifications of tRNA uridine³⁴.

• tRNA-uridine 2-thiolation (bacteria)
• tRNA-uridine 2-thiolation (cytoplasmic)
• tRNA-uridine 2-thiolation (mammalian mitochondria)
• tRNA-uridine 2-thiolation (thermophilic bacteria)
• tRNA-uridine 2-thiolation (yeast mitochondria)

Protein ubiquitination is a process in which target proteins are modified post-translationally by the covalent attachment of ubiquitin, a highly-conserved regulatory protein that is ubiquitously expressed in eukaryotes. Ubiquitination can signal for degradation of the modified protein, alter the protein's cellular location, affect it's activity, and promote or prevent interactions with other proteins. Several similar systems exist in biology in which a small protein, similar to ubiquitin, targets proteins in similar ways. We added three new pathways describing the modifications by the archaeal SAMP (Small Archaeal Modifier Protein), the mycobacterial Pup (Prokaryotic Ubiquitin-like Protein), and the eukaryotic NEDD8 protein (Neural-precursor-cell Expressed Developmentally Down-regulated protein 8).

• protein SAMPylation and SAMP-mediated thiolation
• protein NEDDylation
• protein Pupylation and dePupylation

New Pathways of Microbial Metabolism

Mycobacterium tuberculosis is the causative agent of tuberculosis, one of the major causes of disability and death worldwide. We have added several pathways specific for this organism. One new pathway describes the biosynthesis of GlgE-glycogen - a polymer very similar to eukaryotic glycogen that makes up 80-90% of the organism's capsular layer. Two more pathways describes the in situ activation of two anti-tuberculosis prodrugs - isoniazide and ethionamide, which must be activated within the bacterium. A fourth pathway describes the biosynthesis of phosphatidylinositol mannosides (PIMs), the core of a number of glycolipids that are components of the cell-wall and/or plasma-membrane and are essential for normal growth and viability of the organism. Finally, we added a pathway for protein PUPylation. Pup (for Prokaryotic Ubiquitin-like Protein) is a functional analog of ubiquitin described from members of the Mycobacteria.

• glycogen biosynthesis III (from α-maltose 1-phosphate)
• isoniazid activation
• ethionamide activation
• phosphatidylinositol mannoside biosynthesis
• protein Pupylation and dePupylation (mentioned above)

Biosynthetic Pathways

γ-Butyrolactones are a family of compounds that are produced by the Gram-positive, soil-inhabiting, filamentous bacteria of the genus Streptomyces and serve as chemical signaling molecules or microbial hormones. We added pathways describing the biosynthesis of three of these compounds.

• A-factor γ-butyrolactone biosynthesis
• IM-2 type γ-butyrolactones biosynthesis
• virginiae butanolide type γ-butyrolactones biosynthesis

Another new Streptomyces pathway describes the biosynthesis of coelimycin P1, a polyketide alkaloid that contains an extremely unusual 1,5-oxathiocan-2-one ring system.

• coelimycin P1 biosynthesis

Organisms produce hydrocarbons of different types by different mechanisms. Several mechanisms have been described for the production of hydrocarbons from fatty acids or their intermediates, including synthesis of alkanes from fatty aldehydes by decarbonylation, synthesis of long-chain olefins by head-to head condensation of fatty acids, and production of alkenes from fatty acids by decarboxylation. We revised an existing pathway for the biosynthesis of the cis-alkene carbohydrate hentriaconta-3,6,9,12,15,19,22,25,28-nonaene, which is produced by the bacterium Shewanella oneidensis MR-1, and added a new pathway that describes the generic biosynthesis of cis-alkenes by non-decarboxylative Claisen condensation.

• cis-alkene biosynthesis
• hentriaconta-3,6,9,12,15,19,22,25,28-nonaene biosynthesis

Other biosynthetic pathways were created for the Pseudomonas toxin (2S,3E)-2-amino-4-methoxy-but-3-enoate; the Rhizobia toxin/nodulation enhancer rhizobitoxine; the amino acid L-cysteine; the modified quinone 8-methylmenaquinone; and the cyanobacterial compatible solute glucosylglycerol.

• (2S,3E)-2-amino-4-methoxy-but-3-enoate biosynthesis
• rhizobitoxine biosynthesis
• L-cysteine biosynthesis VII
• 8-methylmenaquinone biosynthesis
• glucosylglycerol biosynthesis

Degradative Pathways

Erythronate and threonate are four-carbon acid sugars that can be used by some bacteria as a carbon source. We added 4 new pathways for their degradation.

• D-erythronate degradation I
• D-erythronate degradation II
• D-threonate degradation
• L-threonate degradation

The detoxification of the highly toxic formaldehyde is a major biochemical necessity for most life forms. We added two more pathways for its degradation, both characterized from Bacillus species.

• formaldehyde oxidation V (bacillithiol-dependent)
• formaldehyde oxidation VII (THF pathway)

A new pathway was added for the degradation of 4,4'-disulfanyldibutanoate, a polythioester used as an alternative monolayer for the manufacture of protein chips that are based on a gold surface. We also revised the trimethylamine (TMA) degradation pathway to reflect the new discovery of the genes encoding dimethylamine monooxygenase.

• 4,4'-disulfanyldibutanoate degradation
• trimethylamine degradation

General Microbial Metabolism

The last reaction in all methanogenic pathways leads to the formation of a mixed disulfide bond between Coenzyme M and Coenzyme B. Different organisms have invented different ways to recycle the CoB-CoM heterodisulfide back to its constituents. We revised the one present pathway and added four new pathways describing this activity.

• coenzyme B/coenzyme M regeneration I (methanophenazine-dependent)
• coenzyme B/coenzyme M regeneration II (ferredoxin-dependent)
• coenzyme B/coenzyme M regeneration III (coenzyme F₄₂₀-dependent)
• coenzyme B/coenzyme M regeneration IV (H₂-dependent)
• coenzyme B/coenzyme M regeneration V (formate-dependent)

Several new pathways describe the construction and recycling of bacterial cell surface components. One pathway describes the biosynthesis of the Escherichia coli O9a O-antigen; another describes an alternative route for recycling of peptidoglycan in organisms that do not have a MurQ enzyme, such as Pseudomonas species; a third pathway describes how pathogens that colonize mucosal tissue decorate their cell wall glycoconjugates with phosphocholine to mimic eukaryotic cell surfaces; and a fourth pathway describes protein lipoylation.

• Escherichia coli serotype O9a O-antigen biosynthesis
• anhydromuropeptides recycling II
• cell-surface glycoconjugate-linked phosphocholine biosynthesis
• protein lipoylation

In inorganic nutrients metabolism we revised the description of the periplasmic nitrate reductase NapAB (EC 1.9.6.1), resulting in a change to the pathway describing an anaerobic respiratory chain comprising glycerol-3-phosphate dehydrogenase and periplasmic nitrate reductase. We have also revised a pathway for thiosulfate oxidation based on the Sox system to reflect new discoveries about the pathway's intermediates.

• nitrate reduction X (dissimilatory, periplasmic)
• thiosulfate oxidation III (multienzyme complex)

New Pathways of Eukaryotic Metabolism

Collagen is a group of naturally occurring animal proteins that form the main component of connective tissue and are the most abundant protein in mammals. The collagen protein is translated in a form known as the pre-propeptide and undergoes several post-translational processing steps.

• procollagen hydroxylation and glycosylation

Homofuraneol is the major flavor component of soy sauce and miso due to its strong, sweet, and caramel-like aroma. A new pathway describes its biosynthesis by yeast.

• homofuraneol biosynthesis

The melleolides are a large family of aryl ester secondary metabolites produced by fungi that belong to the Armillaria genus. Many of them have been shown to inhibit microbial growth and display phytotoxicity. This new pathway describes the biosynthesis of a typical melleolide.

• 6'-dechloromelleolide F biosynthesis

New Pathways specific for Plant Metabolism

We have recently updated all of the pathways that describe the biosynthesis of glucosinolates, secondary metabolites found in 16 plant families that include agriculturally important crop plants of the Brassicaceae family (such as cabbage, mustard, oilseed rape, and broccoli) that are responsible for the typical sharp taste and odor of these plants. Current pathways describe glucosinolates synthesized from methionine, phenylalanine, and tryptophan. We now added a pathway for glucosinolates synthesized from tyrosine.

• glucosinolate biosynthesis from tyrosine

Most flavonoid glycosides are O-glycosides, in which the sugar is linked to the flavonoid skeleton by an oxygen atom. In C-glycosylated flavonoids the anomeric carbon of the sugar is directly bound to an aromatic ring carbon through a C-C bond. Unlike the O-glycosidic bonds, C-glycosidic bonds are resistant to acid hydrolysis and glycosidase cleavage, and thus exhibit different properties from other glycosides. We have revised our current pathway describing C-glucosylation, and added a new pathway for di-C-glucosylation.

• flavonoid di-C-glucosylation
• naringenin C-glucosylation

Pterocarpan phytoalexins are antimicrobial compounds of leguminous plants that are formed upon pathogenic attacks and similar biotic stress-related events. Pisatin is the major phytoalexin in pea, while medicarpin is a major pterocarpan phytoalexin reported from alfalfa, red clover, broad bean, all members of the Trigonella genus, and the model legume Medicago truncatula. We revised their biosynthetic pathways to reflect the discovery of the gene encoding EC 4.2.1.139, medicarpin synthase, which turned out to be a dirigent protein.

• (+)-pisatin biosynthesis
• (-)-medicarpin biosynthesis

The characteristic caramel flavor and mild odor of furaneol and its methylated derivative mesifurane make them the most important flavor compounds in strawberry. We have completely revised the pathway describing their biosynthesis. Another revised pathway describes the biosynthesis of the bisindole alkaloid compounds vindoline and vinblastine, which are produced in Catharanthus roseus (Madagascar periwinkle) leaves and used extensively in cancer chemotherapy. we also revised a pathway describing the formation of volatile esters that are associated with fruity aroma in kiwifruit.

• furaneol and mesifurane biosynthesis
• vindoline and vinblastine biosynthesis
• volatile esters biosynthesis (during fruit ripening)

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of July 2017) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 5959 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 21.0

MetaCyc KB Statistics

Pathways	2526
Reactions	14051
Enzymes	11385
Chemical Compounds	13689
Organisms	2844
Citations	52446
Textbook Page Equivalency	8534

Released on April 28, 2017

New and Updated Pathways

We have added 21_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 17 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 38 new and updated pathways. We also revised one superpathway.

New Pathways of Microbial Metabolism

Most pathogenic bacteria have an absolute requirement for iron, and many obtain it by degrading the host's heme pool. An unexpected variability has been recently found in bacterial heme oxygenases, which are used to break the tetrapyrrole ring and liberate the iron. All of the enzymes consume three molecules of oxygen and a total of seven electron equivalents to catalyze the reaction. However, the enzymes act at different locations on the heme structure, resulting in different products. We have added six new pathways that describe the degradation of heme b by different bacteria.

• heme degradation II
• heme degradation III
• heme degradation IV
• heme degradation V
• heme degradation VI
• heme degradation VII

Another new degradation pathway describes the degradation of ectoine, a compatible solute found in high concentrations in some halophilic microorganisms. Compatible solutes are small molecules that help organisms survive extreme osmotic stress by acting as osmolytes. We also revised pathways describing the degradation of 4-chloronitrobenzene, L-carnitine, and pentachlorophenol.

• ectoine degradation
• 4-chloronitrobenzene degradation
• L-carnitine degradation I
• pentachlorophenol degradation

A new biosynthetic pathway describes the biosynthesis of heme o and heme a, key compounds of the aerobic respiration in mitochondria and bacteria that are used at the dioxygen reduction site of the heme-copper terminal oxidases. Another new pathway covers the biosynthesis of nitric oxide by Gram-positive bacteria. We have also added a second pathway for the biosynthesis of taurine. Two pathways are known for the synthesis of this amino sulfonic acid - the "cysteinesulfinate pathway", which proceeds via 3-sulfinoalanine (see taurine biosynthesis I ), and the "cysteamine pathway", added now, which proceeds via (R)-4'-phosphopantothenoyl-L-cysteine and cysteamine. Another new pathway describes the biosynthesis of roseoflavin, a riboflavin analogue that acts as a powerful antibiotic.

• heme a biosynthesis
• nitric oxide biosynthesis III (bacteria)
• roseoflavin biosynthesis
• taurine biosynthesis II

Other biosynthetic pathways include a new variant pathway for the conversion of urate to allantoin, which involves a recently-discovered fourth type of urate hydroxylase, and revised pathways for the biosynthesis of bacteriochlorophyll e, ectoine, taurine, ubiquinol-10, and factor 420. An extensively revised pathway describes the biosynthesis of factor 430, which was elucidated recently.

• urate conversion to allantoin III
• bacteriochlorophyll e biosynthesis
• ectoine biosynthesis
• factor 420 biosynthesis
• factor 430 biosynthesis
• taurine biosynthesis I
• ubiquinol-10 biosynthesis (prokaryotic)

New Pathways of Eukaryotic Metabolism

(7,8-Dihydropterin-6-yl)methyl diphosphate is the pterin precursor for the biosynthesis of several important cofactors, including tetrahydrofolate, methanopterin and sarcinapterin. We added a new pathway variant that describes its biosynthesis in various taxonomic groups that include Stramenopiles, some microalgae and brown algae, many bacterial phyla, and the malaria parasite Plasmodium falciparum. We also added a new pathway variant that describes the biosynthesis of coenzyme A in eukaryotic organisms, and revised a pathway describing the mitochondrial L-carnitine shuttle.

• 6-hydroxymethyl-dihydropterin diphosphate biosynthesis IV (Plasmodium)
• coenzyme A biosynthesis II (eukaryotic)
• mitochondrial L-carnitine shuttle

New Pathways of Plant Metabolism

The jasmonates are a group of important phytohormones, structurally similar to animal prostaglandins and ubiquitous in the plant kingdom. Many forms exist, based on the structure of jasmonic acid. The jasmonates act as regulatory molecules in many developmental processes that include fertility, sex determination, root elongation and fruit ripening. They are also potent signals activating plant defenses against pathogens, herbivory, wounding and abiotic stress. New and revised pathways include:

• jasmonic acid biosynthesis
• jasmonoyl-amino acid conjugates biosynthesis I
• jasmonoyl-amino acid conjugates biosynthesis II
• jasmonoyl-L-isoleucine inactivation

The ripe cones of the hop plant (Humulus lupulus) are covered with glandular hairs containing a mixture of essential oil and bitter acids. In addition to the great importance of these compounds for the beer brewing industry, owing to their major effect on the final aroma and taste of beer, the bitter acids also have antimicrobial, antifungal and antifeedant activities. New and revised pathways include:

• adlupulone and adhumulone biosynthesis
• colupulone and cohumulone biosynthesis
• lupulone and humulone biosynthesis
• superpathway of bitter acids biosynthesis

Other additions include a new pathway for the biosynthesis of L-pipecolate, an inducer of plant systemic acquired resistance (SAR), and a revised pathway for rubber biosynthesis.

• L-pipecolate biosynthesis
• rubber biosynthesis

Engineered Pathways

We expanded our collection of engineered pathways with a synthetic pathway designed to fix carbon dioxide. The pathway includes enzymes from eight different organisms including one mammal, one plant, five bacteria and one archaeon.

• crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA cycle (engineered)

Other Improvements

Sequence data available for the majority of MetaCyc enzymes

Until now, MetaCyc enzymes did not have sequence data available. Starting with this release, MetaCyc enzymes that have a link to UniProt contain protein sequence information. To retrieve this information, Click on the "Show Sequence at UniProt" command in the operations menu. In addition, it is now possible to perform BLAST searches against MetaCyc proteins with sequence information, using the "BLAST Search" command under the Search menu.

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of February 2017) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database. MetaCyc now contains 5925 EC numbers (including internal M numbers).

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Release Notes for MetaCyc Version 20.5

MetaCyc KB Statistics

Pathways	2507
Reactions	13924
Enzymes	11306
Chemical Compounds	13585
Organisms	2831
Citations	51482
Textbook Page Equivalency	8422

Released on December 17, 2016

New and Updated Pathways

We have added 11_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 20 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 31 new and updated pathways. We also added one new superpathway.

New Pathways of Microbial Metabolism

A new pathway describes a bacterial enzyme that methylates one of the adenine bases in the 23S ribosomal RNA. This single methylation confers resistance to five classes of antibiotics, including the entirely synthetic oxazolidinone antibiotic linezolid, which is often the last line of defense in the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA).

• linezolid resistance

Another new microbial pathway describes the biosynthesis of UDP-yelosamine, an unusual modified sugar precursor that participates in the biosynthesis of the capsular polysaccharide of Bacillus cereus.

• UDP-yelosamine biosynthesis

The Lewis blood group antigens are biosynthetically and structurally related carbohydrate structures found on eukaryotic proteins and sphingolipids (see below). The biosynthesis of Lewis antigens involves fucosylation carried by a number of fucosyltransferases. Remarkably, some human pathogenic bacteria such as Helicobacter pylori expresses complex carbohydrate epitopes on their lipopolysaccharides that are structurally identical to the Lewis blood group antigens and their precursors.

• biosynthesis of Lewis epitopes (H. pylori)

New Pathways of Mammalian Metabolism

We have added several new pathways that describe the complex protein and lipid glycosylation processes that generate the antigens known as histo-blood groups. The most important such system is arguably the one known as the ABO or ABH system, which is best known for being responsible for the A, B and O blood types. The Lewis  system, discovered in 1946, includes the Lewis a, b, x and y epitopes, as well as modified versions of them, which function as markers of cell differentiation and embryonic development. The i/I antigens are found on membrane proteins in red blood cells and many other cell types, as well as various body secretions. The i antigen is very common in fetuses, but undergoes gradual conversion to the I antigen in newborn infants, a process that completes in about 18 months.

The formation of these epitopes, and the enzymes that form them, are described in the pathways:

• ABH and Lewis epitopes biosynthesis from type 1 precursor disaccharide
• ABH and Lewis epitopes biosynthesis from type 2 precursor disaccharide
• i antigen and I antigen biosynthesis

Glycosphingolipids are a family of complex lipids composed of a ceramide and mono- or oligosaccharide moieties that play an important role in various cellular functions including recognition, cell adhesion, proliferation and differentiation. The lipid portion is embedded in the outer plasma membrane leaflet and the sugar chains extend to the outer environment, acting as an antigen. Together with glycoproteins and glycosaminoglycans, the glycosphingolipids contribute to the glycocalyx that covers eukaryotic cell surfaces.

The glycoshphingolipids have been classified into the following 12 series based on their structure: arthro, gala, ganglio, globo, isoglobo, lacto, muco, mollu, neogala, neolacto, schisto, and spirometo. We have added several pathways describing the biosynthesis of the main glycosphingolipid groups:

• gala-series glycosphingolipids biosynthesis
• ganglio-series glycosphingolipids biosynthesis
• globo-series glycosphingolipids biosynthesis
• lacto-series glycosphingolipids biosynthesis
• neolacto-series glycosphingolipids biosynthesis

We also modified the following pathway, which describes different patterns of glycosylation of O-glycans:

• terminal O-glycans residues modification (via type 2 precursor disaccharide)

New Pathways of Plant Metabolism

We have completely revised our coverage of the biosynthesis of several  important groups of plant secondary metabolites.

The glucosinolates are secondary metabolites found in 16 plant families, including agriculturally important crop plants of the Brassicaceae such as cabbage, mustard, oilseed rape, and broccoli, as well as the model plant Arabidposis thaliana, and are responsible for the typical sharp taste and odor of these plants. They are formed from any one of eight amino acids, namely, L-alanine, L-isoleucine, L-leucine, L-methionine, L-phenylalanine, L-tryptophan, L-tyrosine and L-valine. The glucosinolates are stored in the vacuole and come into contact with the enzyme EC 3.2.1.147, thioglucosidase (myrosinase) upon breakage of the cell. The enzyme de-glucosylates the glucosinolates, resulting in formation of nitriles, isothiocyanates and thiocyanates, which are bioactive. Newly updated pathways include:

• aliphatic glucosinolate biosynthesis, side chain elongation cycle
• aromatic glucosinolate activation
• glucosinolate biosynthesis from dihomomethionine
• glucosinolate biosynthesis from hexahomomethionine
• glucosinolate biosynthesis from homomethionine
• glucosinolate biosynthesis from pentahomomethionine
• glucosinolate biosynthesis from phenylalanine
• glucosinolate biosynthesis from tetrahomomethionine
• glucosinolate biosynthesis from trihomomethionine
• glucosinolate biosynthesis from tryptophan
• indole glucosinolate activation (herbivore attack)
• indole glucosinolate activation (intact plant cell)

Cyanogenic glycosides are phytotoxic secondary plant metabolites that are also derived from amino acids, including L-isoleucine, L-leucine, L-phenylalanine, L-tyrosine, L-valine, and cyclopentenyl-glycine. They are found in several thousand plant species including a number of agriculturally important crops such as cassava, sorghum, flax and lotus. Like glucosinolates, cyanogenic glycosides are stored in the vacuole. Under pathogen or herbivore attacks they come in contact with activating enzymes, which release toxic hydrogen cyanide that serves as the first line of chemical defense. Revised pathways include:

• dhurrin biosynthesis
• linamarin biosynthesis
• lotaustralin biosynthesis
• taxiphyllin biosynthesis

We also updated a pathway that describes the biosynthesis of the sugar nucleotide UDP-β-L-rhamnose, produced by most plants (microbes prefer dTDP-β-L-rhamnose), and a pathway for the biosynthesis of camalexin, the main phytoalexin in Arabidopsis thaliana.

• UDP-L-rhamnose biosynthesis
• camalexin biosynthesis

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of November 2016) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

New Superpathways

superpathway of glycosphingolipids biosynthesis

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Release Notes for MetaCyc Version 20.1

MetaCyc KB Statistics

Pathways	2492
Reactions	13791
Enzymes	11250
Chemical Compounds	13395
Organisms	2817
Citations	50741
Textbook Page Equivalency	8272

Released on September 29, 2016

New and Updated Pathways

We have added 38_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 15 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 53 new and updated pathways. We also added one new superpathway.

New Pathways of Microbial Metabolism

Biosynthetic Pathways

• Antibiotics biosynthesis: we added several new pathways describing the biosynthesis of the well-known tetracyclins. We also added a pathway describing one of the resistance mechanisms employed by bacteria against this antibiotic:
  • tetracycline and oxytetracycline biosynthesis
  • chlorotetracycline biosynthesis
  • tetracycline resistance
  We also added a pathway for the biosynthesis of dTDP-L-daunosamine, an unusual sugar that forms a part of the antitumor drug daunorubicin; for the β-lactam antibiotic nocardicin A; and for the tunicamycins, a mixture of related nucleoside antibiotics targeting bacterial teichoic acid and peptidoglycan biosynthesis.
  • dTDP-L-daunosamine biosynthesis
  • nocardicin A biosynthesis
  • tunicamycin biosynthesis

• Teichoic and teichuronic acids: these important polymers make up a significant portion of the cell wall of a wide range of Gram-positive bacteria. We significantly enhanced our coverage of these compounds by revising an existing pathway and adding the following ones:
  • poly(3-O-β-D-glucopyranosyl-N-acetylgalactosamine 1-phosphate) wall teichoic acid biosynthesis
  • poly(ribitol phosphate) wall teichoic acid biosynthesis I (B. subtilis)
  • teichuronic acid biosynthesis (B. subtilis 168)
  • poly(ribitol phosphate) wall teichoic acid biosynthesis II (S. aureus)
  • type I lipoteichoic acid biosynthesis (S. aureus)
  • type IV lipoteichoic acid biosynthesis (S. pneumoniae)

• Sulfur metabolism: we added a pathway for the biosynthesis of dimethyl sulfide from methionine, a Helicobacter pylori pathway for L-cysteine biosynthesis by reverse transsulfuration, and a pathway describing quinone-dependent thiosulfate disproportionation:
  • dimethyl sulfide biosynthesis from methionine
  • L-cysteine biosynthesis VI (from L-methionine)
  • thiosulfate disproportionation III (quinone)

• Other biosynthetic pathways: a new pathway describes the biosynthesis of the bicyclic C50 carotenoid decaprenoxanthin by Corynebacterium glutamicum. Two new pathways, one from yeast and some bacteria, the other from Gram-positive bacteria and archaea, describe the biosynthesis of UMP:
  • decaprenoxanthin and decaprenoxanthin diglucoside biosynthesis
  • UMP biosynthesis II
  • UMP biosynthesis III

Degradation Pathways

• Herbicide degradation: we added pathways describing the degradation of glyphosate (RoundUp), (aminomethyl)phosphonate, and chlorzoxazone, an intermediate in the degradation of fenoxaprop-ethyl (FE).
  • aminomethylphosphonate degradation
  • chlorzoxazone degradation
  • glyphosate degradation I
  • glyphosate degradation II
  • glyphosate degradation III

• Polymer degradation: we added pathways for the degradation of polyethylene terephthalate (PET), the most common thermoplastic polymer resin of the polyester family. The new pathways describe the hydrolysis of the polymer to terephthalate monomers, followed by complete degradation of the monomers:
  • polyethylene terephthalate degradation
  • terephthalate degradation

• Other degradation pathways: chitin is the second most abundant polymer on earth. We expanded our collection of chitin degradation pathways by adding a pathway from Serratia marcescens that utilizes the recently-discovered activity of lytic chitin monooxygenase. We also added a pathway for the degradation of juglone, a toxic compound produced by black walnut trees, and for the degradation of a cyclic tetrasaccharide formed by some bacteria dduring the degradation of starch.
  • chitin degradation III (Serratia)
  • juglone degradation
  • cyclobis-(1→6)-α-nigerosyl degradation

Other New Microbial Pathways of General Interest

• Protein modification: the N-end rules describe how certain proteins are marked for degradation by the identity of their N-terminal residues. In prokaryotes the main degradation machinery is the ClpAP/ClpS serine proteases. We added two pathways that describe modifications of the N-terminus of a protein in order to tag it as a substrate for these degradation systems.
  • N-end rule pathway I (prokaryotic)
  • N-end rule pathway II (prokaryotic)
• Other microbial pathways of interest include an archaeal version of the oxidative branch of the pentose phosphate pathway, and a tRNA splicing pathway that operates in both archaea and some eukaryotes.
  • pentose phosphate pathway (oxidative branch) II
  • tRNA splicing II

New Pathways of Eukaryotic Metabolism

• Just like prokaryotes, eukaryotic organisms also use N-end rules to direct protein degradation (and ubiquitylation). Two such N-rules are described in:
  • Ac/N-end rule pathway
  • Arg/N-end rule pathway (eukaryotic)

• Other eukaryotic pathways describe S-nitrosylation, a post-translational protein modification during which nitric oxide attacks specific cysteine residues in proteins, forming an S-nitrosothiol group, and a new variant of tRNA splicing (a process used to remove introns from tRNA) which is used by metazoa and archaea.
  • protein S-nitrosylation and denitrosylation
  • tRNA splicing II

      New Pathways of Plant Metabolism

• One of the new plant pathways describes the biosynthesis of the unique alkaloids produced by the Amaryllidacea family, which includes galanthamine, an FDA approved drug used for treatment of Alzheimer's disease. The other describes the biosynthesis of the cyanogenic glucosides prunasin and amygdalin, which give the bitter flavor to wild almonds and apricot seeds (among others). Cyanogenic glycosides are defense compounds that are cleaved to toxic hydrogen cyanide upon pathogen or herbivore attacks.
  • Amaryllidacea alkaloids biosynthesis
  • prunasin and amygdalin biosynthesis

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of August 2016) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

List of Additional New and Updated Pathways

New Superpathways

superpathway of tetracycline and oxytetracycline biosynthesis

Updated Pathways

2'-deoxymugineic acid phytosiderophore biosynthesis

2-acetamido-4-amino-2,4,6-trideoxy-α-D-galactosyl-diphospho-ditrans,octacis-undecaprenol biosynthesis

p-cumate degradation to 2-oxopent-4-enoate

p-cymene degradation to p-cumate

actinorhodin biosynthesis

daunorubicin biosynthesis

dhurrin biosynthesis

dimethyl sulfide degradation II (oxidation)

ergothioneine biosynthesis I (bacteria)

mithramycin biosynthesis

molybdenum cofactor biosynthesis

poly(glycerol phosphate) wall teichoic acid biosynthesis

sulfate reduction IV (dissimilatory, to hydrogen sufide))

sulfate reduction V (dissimilatory, to thiosulfate)

thiosulfate disproportionation II (cytochrome)

---

Release Notes for MetaCyc Version 20.0

MetaCyc KB Statistics

Pathways	2453
Reactions	13530
Enzymes	11041
Chemical Compounds	13191
Organisms	2788
Citations	49098
Textbook Page Equivalency	8027

Released on May 5, 2016

New and Updated Pathways

We have added 44_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 21 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 65 new and updated pathways.

New Pathways of Microbial Metabolism

Biosynthetic Pathways

• Bacteriochlorophyll biosynthesis: we have significantly revamped our coverage of bacteriochlorophyll biosynthesis, updating the exiting bacteriochlorophyll a biosynthesis pathway and creating the following new pathways:
  • bacteriochlorophyll b biosynthesis
  • bacteriochlorophyll c biosynthesis
  • bacteriochlorophyll d biosynthesis
  • bacteriochlorophyll e biosynthesis

• Mycobacterial metabolite biosynthesis: mycobacteria are well-known for synthesizing unique compounds not found in other organisms. During this release we created pathways for several important mycobacterial compounds, including:
  • dimycocerosyl phthiocerol biosynthesis
  • dimycocerosyl triglycosyl phenolphthiocerol biosynthesis
  • mycobacterial sulfolipid biosynthesis
  • p-HBAD biosynthesis
  • ω-sulfo-II-dihydromenaquinone-9 biosynthesis
  • phenolphthiocerol biosynthesis

• Antibiotics biosynthesis: new pathways describes the biosynthesis of indolmycin, an antibacterial drug produced by both terrestrial and marine bacteria that exhibits potent antibacterial activity against human pathogens such as Helicobacter pylori and mupirocin-, methicillin-resistant Staphylococcus aureus, and of phosalacine, a herbicidal antibiotic containing L-phophinothricin produced by the soil bacterium Kitasatospora phosalacinea.
  • indolmycin biosynthesis
  • phosalacine biosynthesis

• Other New Microbial Biosynthesis Pathways
  • shinorine biosynthesis. Shinorine is a bacterial sunscreen - a UV-protectant compound produced by bacteria that are exposed to high doses of UV radiation from the sun. See also gadusol biosynthesis for a new eukaryotic sunscreen biosynthetic pathway.
  • 3-hydroxy-4-methyl-anthranilate biosynthesis II
  • heme biosynthesis IV (Gram-positive bacteria)

Degradation Pathways

• Short-chain alkane degradation: the gaseous, short-chain n-alkanes are important contaminants of the atmosphere that originate mostly from natural oil seepage and oil spills. We have added a number of pathways describing their bacterial degradation.
  • butane degradation
  • methyl tert-butyl ether degradation
  • propane degradation I
  • propane degradation II

• Short-chain alkene degradation: we added pathways for the degradation of several important short-chain alkenes, including:
  • ethene and chloroethene degradation
  • isoprene degradation
  • 2-methylpropene degradation

• Bile acids degradation: bile (or gall) is a fluid produced by the liver of most vertebrates that aids in the digestion of lipids in the small intestine. The primary bile acids that are found in bile are converted by bacteria in the large intestine to the secondary bile acids lithocholate and deoxycholate. These, in turn, can be converted to a number of compounds known as iso-bile acids.
  • bile acids degradation
  • iso-bile acids biosynthesis I
  • iso-bile acids biosynthesis II

• Tetritol degradation: we have added a number of pathways that describe the bacterial degradation of tetritols (4-carbon sugar alcohols):
  • L-threitol degradation
  • D-threitol degradation
  • erythritol degradation I
  • erythritol degradation II

• Aromatic compounds degradation: new pathways describe the degradation of bisphenol A (BPA), a widely used plasticizer that has a negative effect on aquatic life; butachlor, a highly stable and persistent herbicide that is one of the top three herbicides used in China; diphenyl ether, the brominated forms of which are widely used as flame retardants and are extremely persistent in soil and water; and γ-resorcylate, an important intermediate in the synthesis of pharmaceuticals and agricultural chemicals.
  • bisphenol A degradation
  • butachlor degradation
  • diphenyl ethers degradation
  • γ-resorcylate degradation I
  • γ-resorcylate degradation II

• Other New Microbial Degradation Pathways
  • leucine degradation IV

Other New Microbial Pathways of General Interest

• carbon monoxide oxidation to CO₂: The pathway that is used by carboxydotrophs, aerobic chemolithoautotrophic bacteria that are able to grow with carbon monoxide as the sole source of both carbon and energy.
• NAD salvage pathway II
• reductive acetyl coenzyme A pathway II (autotrophic methanogens): a new variant of the reductive acetyl-CoA pathway that is used by methanogenic archaea to divert fixed carbon dioxide towards carbohydrate biosynthesis.

New Pathways of Animal Metabolism

• Lipids and Fatty Acids Biosynthesis. Plasmalogens are a unique class of membrane glycerophospholipids that represent up to 20% of the total phospholipid mass in humans and other mammals. We have added pathways that describe both their biosynthesis and degradation.
  • plasmalogen biosynthesis
  • plasmalogen degradation

• Other animal pathways
  • gadusol biosynthesis. Gadusol is a eukaryotic sunscreen - a UV-protectant compound produced by egg-laying vertebrates that protects them from high doses of UV radiation from the sun. See also shinorine biosynthesis for a new bacterial sunscreen biosynthetic pathway.

New Pathways of Plant Metabolism

• Biosynthetic Pathways. A new plant pathway describes the biosynthesis of chlorophyll a via a pathway that utilizes the enzyme 3,8-divinyl protochlorophyllide a 8-vinyl-reductase (ferredoxin). This enzyme has been described in cyanobacteria, Euglenozoa, Stramenopiles, and green and red algae. We also added pathways for the biosynthesis of yatein, a typical lignan component of heartwood in angiosperm trees that serves as a long-term protectant against pathogen attacks, and 4'-desmethyl-epipodophyllotoxin, the direct precursor to etoposide, a topoisomerase II inhibitor that is used used in various chemotherapies, including lung cancer, lymphomas, and genital tumors.
  • chlorophyll a biosynthesis III
  • yatein biosynthesis I
  • (-)-4'-desmethyl-epipodophyllotoxin biosynthesis

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of March 2016) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

List of Updated Pathways

Updated Pathways

(-)-dehydrodiconiferyl alcohol degradation

2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis

3,8-divinyl-chlorophyllide a biosynthesis II (anaerobic)

4-hydroxy-2(1H)-quinolone biosynthesis

bile acids degradation

anthocyanin biosynthesis

bacteriochlorophyll a biosynthesis

chlorophyll a biosynthesis I

cholesterol degradation to androstenedione II (cholesterol dehydrogenase)

dibenzothiophene desulfurization

hinokinin biosynthesis

hydrogen production VI

matairesinol biosynthesis

methanogenesis from methylthiopropanoate

nucleoside and nucleotide degradation (archaea)

phenazine-1-carboxylate biosynthesis

proanthocyanidins biosynthesis from flavanols

resorcinol degradation

thiamine diphosphate biosynthesis III (Staphylococcus)

validamycin biosynthesis

yatein biosynthesis II

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Release Notes for MetaCyc Version 19.5

MetaCyc KB Statistics

Pathways	2411
Reactions	13074
Enzymes	10789
Chemical Compounds	12792
Organisms	2740
Citations	47838
Textbook Page Equivalency	7773

Released on November 12, 2015

New and Updated Pathways

We have added 60_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 12 pathways by adding commentary and updated enzyme and gene information, for a total of 72 new and updated pathways. Of the new pathways, one was contributed by EcoCyc curators. We also added two new superpathways and updated two existing superpathways.

New Pathways of Microbial Metabolism

Biosynthetic Pathways

• iron-molybdenum cofactor biosynthesis describes the biosynthesis of the iron-molybdenum cofactor of nitrogenase.
• 5,6-dimethylbenzimidazole biosynthesis II (anaerobic) describes an anaerobic pathway for 5,6-dimethylbenzimidazole, the lower ligand of cobalamin.
• lyngbyatoxin biosynthesis describes the synthesis of a cyanobacterial secondary product that causes swimmer itch.
• CMP-diacetamido-8-epilegionaminic acid biosynthesis describes the synthesis of a component of the O-antigen of Escherichia coli O108.
• sch210971 and sch210972 biosynthesis. These fungal secondary metabolites have been shown to inhibit the chemokine receptor CCR-5 of the human immune system.
• 4-hydroxy-4-methyl-L-glutamate biosynthesis. This unique amino acid is incorporated into sch210971 and sch210972.
• The following pathways describe the biosynthesis of red pigments contributing color, reinforcement and protection against UV-radiation for the asexual fungal spores known as conidia as well as the fruiting body.
  • 8-O-methylfusarubin biosynthesis
  • bikaverin biosynthesis
  • aurofusarin biosynthesis
  • citreoisocoumarin and bikisocoumarin biosynthesis
• stipitatate biosynthesis. Stipitatate, formed by the fungus Talaromyces stipitatus, contains the unusual seven-membered aromatic ring system known as the tropolone structure.
• viridicatin biosynthesis
• 4'-methoxyviridicatin biosynthesis
• methyl phomopsenoate biosynthesis
• The following pathways describe the biosynthesis of sesterterpenoids, formed from five isoprene units (C25), which are rather rare in nature. Their biosynthesis employs chimeric cyclases that are able to catalyze rather complex conversions.
  • ophiobolin F biosynthesis
  • stellatic acid biosynthesis

The following pathways describe the biosynthesis of various trichothecenes, which are sequiterpenoids characterized by a varying pattern of oxygen and ester groups on a core tricyclic skeleton bearing an epoxide function. The main producers of trichothecenes are fungi of the genus Fusarium.

• calonectrin biosynthesis
• harzianum A and trichodermin biosynthesis
• nivalenol biosynthesis
• deoxynivalenol biosynthesis
• T-2 toxin biosynthesis

Antibiotics Biosynthesis:

• actinomycin D biosynthesis describes the biosynthesis of Actinomycin D, the first antibiotic obtained in pure form from an actinomycete, and the first antibiotic shown to have anti-cancer activity.
• 3-hydroxy-4-methyl-anthranilate biosynthesis. While not an antibiotic per se, 3-hydroxy-4-methyl-anthranilate serves as a building block of the actinomycin phenoxazinone chromophore.
• holomycin biosynthesis. Holomycin belongs to the dithiopyrrolones, a family of antibiotics that are characterized by an electronically unique bicyclic structure, which contains a compact disulfide bridge between two ene-thiols. They exhibit a very broad-spectrum antibiotic activity and potent antiangiogenic effects.
• guadinomine B biosynthesis. Guadinomine B is a member of the guadinomines, anti-infective compounds that are also the most potent known inhibitors of the type III secretion system of Gram-negative bacteria.
• dapdiamides biosynthesis. Dapdiamides consist of fumaramoyl and epoxysuccinamoyl dipeptides, and attack the enzyme EC 1.1.1.34, glutamine-fructose-6-phosphate transaminase, disrupting cell wall biosynthesis.
• penicillin G and penicillin V biosynthesis. These antibiotics are produced by filamentous fungi of the genera Penicillium and Aspergillus.
• zwittermicin A biosynthesis. Zwittermicin A is a very unusual molecule and one of only a few linear aminopolyols that were identified in nature. It is synthesized by a polyketide synthase as a larger construct that is later cleaved on both sides.
• Quinomycin-type antibiotics are C2-symmetric cyclic depsipeptides with a pair of intercalative chromophores that show potent antibacterial, anticancer and antiviral activities. Two new pathways describe the biosynthesis of three of those.
  • echinomycin and triostin A biosynthesis
    
  • thiocoraline biosynthesis
• The following two pathways describe the synthesis of the chromophore component of the quinomycin-type antibiotics:
  • 3-hydroxyquinaldate biosynthesis
  • quinoxaline-2-carboxylate biosynthesis
• dTDP-D-ravidosamine and dTDP-4-acetyl-D-ravidosamine biosynthesis. While not an antibiotic on its own, D-ravidosamine is a modified sugar found in the antibiotic ravidomycin V.

Lipids and Fatty Acids Biosynthesis

• 10,13-epoxy-11-methyl-octadecadienoate biosynthesis. This pathway describes the synthesis of the furan-containing fatty acid 10,13-epoxy-11-methyl-octadecadienoate, which is found in Rhodobacter sphaeroides.
• α-diglucosyldiacylglycerol biosynthesis. α-Diglucosyldiacylglycerol is a major componenet of the bilayer membrane of the bacterium Acholeplasma laidlawii, which lacks cell walls.
• Three new pathways describe the biosynthesis of unusual lipids produced by Mycobacteria.
  • polyacyltrehalose biosynthesis. Polyacyltrehaloses are a family of polymethyl-branched fatty acid-containing trehalose esters that populate the outer membrane of Mycobacteria;
  • β-D-mannosyl phosphomycoketide biosynthesis
  • phthiocerol biosynthesis. Phthiocerols are important members of the mycobacterial cell wall outer layer. They are esterified by mycocerosic or phthioceranic acids.

Degradation Pathways

• sulfoquinovose degradation II. a novel pathway for the degradation of sulfoquinovose by some Pseudomonas species.
• L-malate degradation I
• L-malate degradation II

Aromatic Compounds Degradation

• 1-chloro-2-nitrobenzene degradation
• 2,4-xylenol degradation to protocatechuate
• 2,5-xylenol and 3,5-xylenol degradation
• 4-methylphenol degradation to protocatechuate

Other New Microbial Pathways of General Interest

• bacterial bioluminescence
• nitrite reduction (hemoglobin)

New Pathways of Animal Metabolism

Lipids and Fatty Acids Biosynthesis

• (4Z,7Z,10Z,13Z,16Z)-docosa-4,7,10,13,16-pentaenoate biosynthesis (6-desaturase). This pathway describes the production of this very-long-chain polyunsaturated fatty acid via the well-established 6-desaturase activity of the mammalian FADS2 enzyme.
• The following pathways describe the production of several very-long-chain polyunsaturated fatty acids based on newly-discovered 4- and 8-desaturase activities of the human FADS2 enzyme.
  • (4Z,7Z,10Z,13Z,16Z)-docosa-4,7,10,13,16-pentaenoate biosynthesis II (4-desaturase)
  • docosahexaenoate biosynthesis IV (4-desaturase, mammals)
  • arachidonate biosynthesis V (8-detaturase, mammals)
  • icosapentaenoate biosynthesis III (8-desaturase, mammals)

New Pathways of Plant Metabolism

Secondary Metabolite Biosynthesis

• Anthocyanin sambubioside and acylated sambubioside belong to a group of vacuolar pigments that contribute to flower colors as attractants for pollinators, are able to scavenge radicals, and represent valued food colorants with antioxidant and chemoprotective properties.
  • anthocyanidin acylglucoside and acylsambubioside biosynthesis
  • anthocyanidin sambubioside biosynthesis
• geranyl β-primeveroside biosynthesis. This monoterpenoid is the most prevalent aroma diglycoside storage form found in the tea-plant Camellia sinensis, the source for the most consumed beverage worldwide.
• arabidopyrone biosynthesis. This pathway, which describes a novel group of substituted α-pyrones in Arabidopsis thaliana, exemplifies a new evolutionary line descendent from the core phenylpropanoid pathway.
• (3R)-linalool biosynthesis. Linalool is an acyclic monoterpene alcohol with a pleasant fragrance associated with a diverse array of plants.
• aucuparin biosynthesis. Aucuparin is a phytoalexin found only in the Maloideae, a subfamily of the rose family that includes fruit crops (apple, pear, cherry, peach and others) and highly valued ornamental plants such as rowan, rose and hawthorn.
• carnosate bioynthesis. Carnosate is a benzenediol abietane diterpene synthesized by some members of the Lamiaceae family that has strong antioxidant, anti-inflammatory, and anticancer properties.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of October 2015) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

List of Additional New and Updated Pathways

New Pathways from EcoCyc

N⁶-L-threonylcarbamoyladenosine³⁷-modified tRNA biosynthesis

New Superpathways

superpathway of photosynthetic hydrogen production

superpathway of trichothecene biosynthesis

Updated Pathways

3,6-anhydro-α-L-galactopyranose degradation

CMP-3-deoxy-D-manno-octulosonate biosynthesis

betacyanin biosynthesis

betalamic acid biosynthesis

chitin biosynthesis

di-trans,poly-cis-undecaprenyl phosphate biosynthesis

formate assimilation into 5,10-methylenetetrahydrofolate

glycogen biosynthesis I (from ADP-D-Glucose)

hopanoid biosynthesis (bacteria)

isovitexin glycosides biosynthesis

phosphinothricin tripeptide biosynthesis

phylloquinol biosynthesis

Updated Superpathways

superpathway of linalool biosynthesis

superpathway of phylloquinol biosynthesis

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Release Notes for MetaCyc Version 19.1

MetaCyc KB Statistics

Pathways	2363
Reactions	12701
Enzymes	10517
Chemical Compounds	12362
Organisms	2694
Citations	46117

Released on June 25th, 2015

New and Updated Pathways

We have added 56_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 43 pathways by adding commentary and updated enzyme and gene information, for a total of 99 new and updated pathways. Of the new pathways, 7 were contributed by EcoCyc curators. We also updated one superpathway.

Microbial Metabolism: In fatty acid metabolism, we added new pathways for the anaerobic biosynthesis of oleate, studied in the bacteria Aerococcus viridans and Clostridium beijerinckii, of the epoxy fatty acid gondoate, also produced by Aerococcus viridans, and of 5-hexynoate, an unusual fatty acid that contains a terminal triple bond, produced by the cyanobacterium Moorea producens. We also revised pathways describing the biosynthesis of the unsaturated fatty acid (5Z)-dodec-5-enoate, adding the FabN and FabO enzymes from Enterococcus faecalis and FabM from Streptococcus pneumonia. We added a pathway for the biosynthesis of galactolipids in cyanobacteria, which differs from the pathway used by plants. Two new pathways describe the attachment of 3-deoxy-D-manno-octulosonate (Kdo) or its 8-aminated derivative to lipid IV_A during the synthesis of lipopolysaccharides in the bacteria Haemophilus influenza and Shewanella oneidensis, respectively. In sulfur metabolism we updated the pathways for thiosulfate oxidation via tetrathionate and for intracellular sulfur oxidation to reflect new discoveries in the field, and we similarly updated the pathway for cholesterol degradation by Mycobacteria. We have extensively revised the pathways describing the biosynthesis and degradation of the important polysaccharide alginate, and added degradation pathways for the polysaccharide ulvan and the glycosaminoglycans heparin, heparan sulfate, dermatan sulfate, and hyaluronan. In antibiotic biosynthesis we added pathways for rosamicin, a 16-member macrolide antibiotic produced by the bacterium Micromonospora rosaria, and for saframycin A, a member of the tetrahydroisoquinoline class of antibiotics that is produced by Streptomyces lavendulae. We have also added two pathways describing N-glycosylation in the archaea Haloferax volcanii and Methanococcus voltae.

Several new fungal pathways cover the formation of important polyketide mycotoxins and antibiotics including griseofulvin, dechlorogriseofulvin, equisetin, fusaridione A, fusarin C, fusaric acid and viridicatumtoxin. Griseofulvin has been widely used for treatment of dermatophytes. The unique pharmacological properties of equisetin prompted the development of the first licensed HIV integrase inhibitor (raltegravir). Viridicatumtoxin is a very potent growth inhibitor of antibiotic-resistant Staphylococcus aureus, fusarin C is considered a mutagenic contaminant of human food and livestock feed, and fusaric acid has been used as cytotoxin towards various human cancer cell lines and inhibitor of the HIV-1 transactivator protein tat, indicating a therapeutic potential for the treatment of HIV-1 dementia. A new fungal pathway describes the biosynthesis of echinocandin B, a lipopeptide antibiotic exhibiting fungicidal and fungistatic properties against ascomycetes of the genera Candida and Aspergillus. We also added pathways for several cyclopeptides. Aureobasidin A is a cyclic peptide that possesses antifungal activity due to its ability to inhibit the synthesis of sphingolipidss. It is also used in the biological control of postharvest pathogens. Apicidin is a mycotoxin cyclopeptide best known for its antiprotozoal activity against Apicomplexa, which, amongst others, cause malaria. Apicidin F is a mycotoxin cyclopeptide produced only in Fusarium fujikuroi, the causative agent of the infamous bakanae (foolish seedling) disease. Finally, we added a pathway for the biosynthesis of the fungal alkaloid tryptoquialanine, which is known for its tremorgenic properties and potential to elucidate processes regarding neurotransmitter release on neuronal synapses

Animal Metabolism: We added pathways for the biosynthesis of several pheromones produced by the moth Spodoptera littoralis, and for (8E,10E)-dodeca-8,10-dienol, the major pheromone component of the codling moth Cydia pomonella. We also revised and enhanced the pathway describing N-glycosylation in yeast.

Plant Metabolism: New plant secondary metabolite pathways involved in the biosynthesis of lignans, norlignans, carotenoids and phenylpropanoids have been added to MetaCyc. Lignans such as yatein, pluviatolide and arctigenin are components of heartwood and together with the norlignan hinokiresinol are involved in resistance against pathogenic attacks. The lignan arctigenin is also pharmacologically active and used as drug in treatments against rheumatic arthritis, gynopathic disorders and type 2 diabetes. The plant pathway for the biosynthesis of the ketocarotenoid pigment astaxanthin, also found in bacteria and fungi, has been added as was a degradation pathway for the phytoalexin kievitone. Another pathway describes the biosynthesis of the isoflavonoid calycosin and its glucosidic derivatives, which have been found as main constituents in traditional Chinese medicine (TCM) and are efficiently employed as antiperspirants, immunostimulants, and in cancer therapies. Two new pathways, neophaseic acid biosynthesis and 7'-hydroxyabscisate biosynthesis, provide insight into the regulation of the plant hormone abscisic acid (ABA), and the pathway of coniferyl alcohol 9-methyl ester, a rare compound in nature, sheds light on potential intermediates in the metabolic grid of aryltetralin lignins. We also revised pathways describing the biosynthesis of the epoxy fatty acid sterculate by Sterculia foetida, and of ccrepenynate, a fatty acid that contains an unusual acetylenic (triple) bond that is found in high concentration in Crepis alpina seed oil.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of June 2015) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

List of New and Updated Pathways

New Pathways

2,2'-dihydroxyketocarotenoids biosynthesis

3-hydroxy-L-homotyrosine biosynthesis

4-methyl-proline biosynthesis

5-hexynoate biosynthesis

7'-hydroxyabscisate biosynthesis

(8E,10E)-dodeca-8,10-dienol biosynthesis

apicidin biosynthesis

apicidin F biosynthesis

arctigenin and isoarctigenin biosynthesis

astaxanthin biosynthesis (flowering plants)

aureobasidin A biosynthesis

bis(guanylyl molybdenum cofactor) biosynthesis

calycosin 7-O-glucoside biosynthesis

CMP-8-amino-3,8-dideoxy-D-manno-octulosonate biosynthesis

coniferyl alcohol 9-methyl ester biosynthesis

dechlorogriseofulvin biosynthesis

dermatan sulfate degradation I (bacterial)

dTDP-β-L-digitoxose biosynthesis

echinenone and zeaxanthin biosynthesis (Synechocystis)

echinocandin B biosynthesis

echinocandin B degradation

equisetin biosynthesis

fusaric acid biosynthesis

fusaridione A biosynthesis

fusarin C biosynthesis

galactolipid biosynthesis II

glycogen degradation III (via anhydrofructose)

gondoate biosynthesis (anaerobic)

griseofulvin biosynthesis

heparan sulfate degradation

heparin degradation

hinokiresinol biosynthesis

hyaluronan degradation

Kdo transfer to lipid IV_A II

Kdo8N transfer to lipid IV_A

kievitone detoxification

neophaseic acid biosynthesis

oleate biosynthesis IV (anaerobic)

pluviatolide biosynthesis

protein N-glycosylation (Haloferax volcanii)

protein N-glycosylation (Methanococcus voltae)

rosamicin biosynthesis

saframycin A biosynthesis

Spodoptera littoralis pheromone biosynthesis

tryptoquialanine biosynthesis

ulvan degradation

vernolate biosynthesis II

viridicatumtoxin biosynthesis

yatein biosynthesis

New Pathways from EcoCyc

glycerol-3-phosphate to fumarate electron transfer

hydrogen to dimethyl sulfoxide electron transfer

hydrogen to fumarate electron transfer

hydrogen to trimethylamine N-oxide electron transfer

nitrate reduction IX (dissimilatory)

nitrate reduction X (periplasmic, dissimilatory)

peptidoglycan maturation (meso-diaminopimelate containing)

Updated Pathways

1,5-anhydrofructose degradation

4-deoxy-L-threo-hex-4-enopyranuronate degradation

(5Z)-dodec-5-enoate biosynthesis

abscisic acid glucose ester metabolism

alginate biosynthesis I (algal)

alginate biosynthesis II (bacterial)

alginate degradation

astaxanthin biosynthesis (bacteria, fungi, algae)

cholesterol degradation to androstenedione II (cholesterol dehydrogenase)

crepenynate biosynthesis

cutin biosynthesis

daunorubicin biosynthesis

esculetin biosynthesis

ethylmalonyl-CoA pathway

formate to trimethylamine N-oxide electron transfer

fumiquinazoline D biosynthesis

galactolipid biosynthesis I

glycogen degradation II (eukaryotic)

L-glutamate degradation V (via hydroxyglutarate)

maackiain biosynthesis

mannitol cycle

NADH to cytochrome bd oxidase electron transfer I

NADH to cytochrome bo oxidase electron transfer I

NADH to fumarate electron transfer

NADH to trimethylamine N-oxide electron transfer

nicotine degradation II (pyrrolidine pathway)

nicotine degradation III (VPP pathway)

nitrate reduction III (dissimilatory)

nitrate reduction VIII (dissimilatory)

nostoxanthin biosynthesis

pisatin biosynthesis

protein N-glycosylation (eukaryotic, high mannose)

pterocarpan phytoalexins modification (maackiain, medicarpin, pisatin, phaseollin)

raspberry ketone biosynthesis

resveratrol biosynthesis

sporopollenin precursors biosynthesis

sterculate biosynthesis

succinate to cytochrome bd oxidase electron transfer

succinate to cytochrome bo oxidase electron transfer

sulfur oxidation IV (intracellular sulfur)

thiosulfate oxidation II (via tetrathionate)

vernolate biosynthesis I

vernolate biosynthesis III

Updated Superpathways

superpathway of pterocarpan biosyntheis (via formononetin)

---

Release Notes for MetaCyc Version 19.0

MetaCyc KB Statistics

Pathways	2310
Reactions	12377
Enzymes	10298
Chemical Compounds	11987
Organisms	2668
Citations	44878

Released on March 19, 2015

New and Updated Pathways

We have added 66_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 37 pathways by adding commentary and updated enzyme and gene information, for a total of 103 new and updated pathways. Of the new pathways, 4 were contributed by EcoCyc curators. We also added 3 new superpathways.

Microbial Metabolism: We have added several new pathways for microbial polyunsaturated fatty acids (PUFA) biosynthesis. Although best studied in eukaryotes, PUFAs are also found in phytoplankton and in some deep sea bacteria. Microbial PUFA biosynthesis has been documented for arachidonate, docosahexaenoate (DHA), and icosapentaenoate (EPA).

We also expanded and revised our coverage of phytobilin biosynthesis. Phytobilins are tetrapyrroles that serve as chromophores of phycobiliproteins, which are components of the photosynthetic light-harvesting antenna complexes of cyanobacteria and some algae. Phytobilins are also found in the phytochromes of green plants. MetaCyc now contains the full complement of pathways for synthesizing all known phytobilins - phycocyanobilins, phycoerythrobilins, phycourobilin, phycoviolobilin, and phytochromobilin.

Several bacterial pathways for the biosynthesis of antibiotic and antifungal compounds have been added. These include bacilysin in Bacillus subtilis and nystatin, blasticidin S, and arginomycin from Streptomyces species. A candicidin biosynthetic pathway in Streptomyces was also significantly revised. In addition we curated a biosynthetic pathway for the antibiotic bacimethrin, which is converted by some bacteria to a thiamin antivitamin.

In bacterial members of the human gut microbiome we added a novel pathway for degradation of the rare sugar L-galactose, a variant of N-acetylneuraminate and N-acetylmannosamine degradation found in the genus Bacteroides, a pathway involving a unique ATP-conserving phosphorylase that is involved in N-glycan degradation, and a pathway for formation of the beneficial bile salt ursodeoxycholate.

We also added several biosynthetic pathways for nucleotide-activated sugars that become incorporated into bacterial surface glycans. These include GDP-6-deoxy-D-altro-heptose from Campylobacter jejuni, GDP-6-deoxy-D-manno-heptose from Yersinia pseudotuberculosis, and UDP-galactofuranose. The sugar D-galactofuranose is incorporated into the surface glycans of some pathogenic bacteria, fungi, protists and nematodes, but not mammals.

Other new bacterial pathways include oxidation of the xenobiotic mercaptosuccinate by a soil bacterium; a methanol dissimilation pathway proposed for the industrially important Corynebacterium glutamicum; and the biosynthesis of okenone, a ketocarotenoid with unique light absorption and photoprotection properties found in many purple sulfur bacteria. We also added several new electron transport and transfer pathways from EcoCyc. In archaea an important pathway for the biosynthesis of methanofuran has been extensively revised to reflect newly available data.

In fungal primary metabolism, we added a modified β-oxidation pathway for propanoyl-CoA degradation in Candida albicans. In fungal secondary metabolism we added biosynthetic pathways for the polyketides tenellin and bassianin from Beauveria bassiana, and aspyridone A from Aspergillus nidulans; the siderophores ferrichrome and ferrichrome A; the meroterpenoid anditomin; and the tremorgenic diterpenoid lolitrem B that is pathogenic in grazing animals, but bioprotective to ryegrass (Lolium perenne). New fungal alkaloid biosynthetic pathways include the insect deterrent peramine, the anticancer compound stephacidin A, the bioactive compounds notoamide C and notoamide D, and the cytochalasan chaetoglobosin A. Also included are the diketopiperazine alkaloids roquefortine C, meleagrin and neoxaline that are known food contaminants but are also of medicinal interest. In addition, we added a pathway for detoxification of the major plant phytoalexins maackiain, medicarpin, pisatin and phaseollin by phytopathogenic fungi.

Animal Metabolism: A major topic that we revised for this release is the biosynthesis of polyunsaturated fatty acids. The key enzymes in this process are the desaturases, which use molecular oxygen to introduce a double bond into fatty acids incorporated into lipids or coenzyme A. Different organisms have different types of desaturases, and synthesize these compounds by different routes, which can involve elongation and β-oxidation in addition to desaturation. Our coverage has been expanded to include all known animal desaturases. In addition to revising the existing pathways, we added two new pathways for arachidonate biosynthesis that involve either 6- and 5-desaturases, or 8- and 5-desaturases, and a mammalian docosahexaenoate biosynthesis pathway that involves a 6-desaturase (lower eukaryotes synthesize docosahexaenoate in a pathway that involves a 4-desaturase).

Plant Metabolism: As was done for animal metabolism, we extensively revised pathways for the biosynthesis of plant unsaturated fatty acids. In addition to the common oleate, palmitoleate, linoleate, α-linolenate, and γ-linolenate, plants are known to produce a number of unique unsaturated fatty acids. We have revised or created pathways for the production of sapienate, (5Z)-icos-5-enoate, petroselinate, (9Z,12Z)-octadecadien-6-ynoate, dicranin, juniperonate, sciadonate, vernolate, ricinoleate, calendate, dimorphecolate, punicate, α-eleostearate, pinolenate and coniferonate. Another revised area is the metabolism of volatile organic sulfur compounds found in members of the Allioideae family (such as onion, garlic, chives and leek), including alliin, methiin, propanethial S-oxide, and (Z)-butanethial-S-oxide, as well as the related (Z)-phenylmethanethial S-oxide, which is produced by the non-allium Petiveria alliacea

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of February 2015) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

List of New and Updated Pathways

New Pathways

2,4,6-trinitrophenol and 2,4-dinitrophenol degradation

2,4-dinitroanisole degradation

3,6-anhydro-α-L-galactopyranose degradation

(7Z,10Z,13Z)-hexadecatrienoate biosynthesis

α-linolenate biosynthesis II (cyanobacteria)

anditomin biosynthesis

arachidonate biosynthesis II (bacteria)

arachidonate biosynthesis III (metazoa)

arachidonate biosynthesis IV (8-detaturase)

arginomycin biosynthesis

aspyridone A biosynthesis

astaxanthin dirhamnoside biosynthesis

autoinducer AI-2 degradation

autoinducer CAI-1 biosynthesis

β-1,4-D-mannosyl-N-acetyl-D-glucosamine degradation

bacilysin biosynthesis

bacimethrin and bacimethrin pyrophosphate biosynthesis

bassianin and desmethylbassianin biosynthesis

blasticidin S biosynthesis

chaetoglobosin A biosynthesis

docosahexaenoate biosynthesis II (bacteria)

docosahexaenoate biosynthesis III (mammals)

ferrichrome A biosynthesis

ferrichrome biosynthesis

γ-linolenate biosynthesis III (cyanobacteria)

GDP-6-deoxy-D-altro-heptose biosynthesis

GDP-6-deoxy-D-manno-heptose biosynthesis

GDP-mycosamine biosynthesis

icosapentaenoate biosynthesis V (Δ8 desaturase)

juniperonate biosynthesis

L-galactose degradation

L-gulonate degradation

linoleate biosynthesis III (cyanobacteria)

lolitrem B biosynthesis

meleagrin biosynthesis

mercaptosuccinate degradation

methanol oxidation to carbon dioxide

methiin metabolism

methylerythritol phosphate pathway II

N-acetylneuraminate and N-acetylmannosamine degradation II

naphthalene degradation (anaerobic)

neoxaline biosynthesis

nitrogen fixation II (flavodoxin)

notoamide C and D biosynthesis

nystatin biosynthesis

okenone biosynthesis

oleate biosynthesis III (cyanobacteria)

palmitoleate biosynthesis III (cyanobacteria)

peramine biosynthesis

phosphatidylinositol biosynthesis II (eukaryotes)

phycoerythrobilin biosynthesis II

phycourobilin biosynthesis

phycoviolobilin biosynthesis

propanoyl-CoA degradation II

pterocarpan phytoalexins modification (maackiain, medicarpin, pisatin, phaseollin)

ricinoleate biosynthesis

roquefortine C biosynthesis

stearidonate biosynthesis (cyanobacteria)

stephacidin A biosynthesis

tenellin biosynthesis

UDP-galactofuranose biosynthesis

ursodeoxycholate biosynthesis (bacteria)

New Pathways from EcoCyc

D-lactate to cytochrome bo oxidase electron transport

glycerol-3-phosphate to cytochrome bo oxidase electron transfer

NADH to cytochrome bd oxidase electron transport II

NADH to cytochrome bo oxidase electron transfer II

New Superpathways

superpathway of candicidin biosynthesis

superpathway of roquefortine, meleagrin and neoxaline biosynthesis

superpathway of stearidonate biosynthesis (cyanobacteria)

Updated Pathways

4-aminobenzoate biosynthesis

α-eleostearate biosynthesis

alliin metabolism

aspirin triggered resolvin D biosynthesis

C4 photosynthetic carbon assimilation cycle, NAD-ME type

C4 photosynthetic carbon assimilation cycle, NADP-ME type

C4 photosynthetic carbon assimilation cycle, PEPCK type

calendate biosynthesis

candicidin biosynthesis

D-galacturonate degradation II

D-glucuronate degradation II

Δ5-eicosenoate biosynthesis

dicranin biosynthesis

dimorphecolate biosynthesis

docosahexaenoate biosynthesis I (lower eukaryotes)

enterobactin biosynthesis

ethiin metabolism

gliotoxin inactivation

hispidol and hispidol glucoside biosynthesis

hydroxylated fatty acid biosynthesis (plants)

linoleate biosynthesis I (plants)

L-proline betaine degradation

methanofuran biosynthesis

phycocyanobilin biosynthesis

phycoerythrobilin biosynthesis I

pinolenate acid and coniferonate acid biosynthesis

propanethial S-oxide biosynthesis

punicate biosynthesis

resolvin D biosynthesis

ricinoleate biosynthesis

sciadonate biosynthesis

starch degradation I

stigma estolide biosynthesis

superpathway of Allium flavor precursors

UDP-N-acetyl-α-D-galactosaminuronate biosynthesis

(Z)-butanethial-S-oxide biosynthesis

(Z)-phenylmethanethial S-oxide biosynthesis

---

Release Notes for MetaCyc Version 18.5

MetaCyc KB Statistics

Pathways	2255
Reactions	12074
Enzymes	10100
Chemical Compounds	11681
Organisms	2579
Citations	43818

Released on November 7, 2014

The text contained within the mini-review summaries for MetaCyc pathway, enzyme, and metabolite pages is the equivalent of 6,300 textbook pages. This information was curated from 44,000 publications.

New and Updated Pathways

We have added 58_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 24 pathways by adding commentary and updated enzyme and gene information, for a total of 82 new and updated pathways. Of the new pathways, 7 were contributed by EcoCyc curators and 6 were contributed by HumanCyc curators. We also added one new superpathway.

Microbial Metabolism: We have added a number of bacterial biosynthetic pathways including a new variant of heme biosynthesis characterized in archaea and Desulfovibrionales, a pathway for the biosynthesis of heme d₁, which is only made by denitrifying bacteria with a cytochrome nitrite reductase cd1 (nirS), a pathway for production of a disaccharide present in the O-antigen of the pathogens Escherichia coli O5 and E. coli O104, which produce Shiga-like toxins, a pathway for the biosynthesis of prodigiosin, a red linear tripyrrole antibiotic produced by some strains of Serratia and related species, and a new variant of folate biosynthesis that operates in Chlamydia. We also added biosynthetic pathways found in Bacilli for the anti-fungal antibiotics rhizocticin A and rhizocticin B that contain the non-proteinogenic amino acid L-2-amino-5-phosphono-3-cis-pentenoate, and for mannojirimycin, an intermediate in the pathway leading to nojirimycin antibiotics. Other pathways describe the synthesis of the thiooctose moiety of the antibiotic lincomycin A, the synthesis of a 2-amino-3-hydroxycyclopent-2-enone moiety found in many secondary metabolites, and the polyketide pigments flaviolin dimer and mompain that protect organisms from ultraviolet radiation. Additional biosynthetic pathways were added for cardiolipin and phosphatidylethanolamine in Xanthomonas, a sialic acid derivative found in the fish pathogen Allivibrio salmonicida, and a second archaeal variant of the mevalonate pathway.

In bacterial degradation we curated a pathway for dehydrodiconiferyl alcohol degradation, one of the major dilignols generated in lignifying xylem, and a tyrosine degradation pathway in gut clostridia that produces 4-methylphenol. This compound is sulfated in the liver of the bacterium's animal host to toxic 4-methylphenyl sulfate. We also added novel pathways for trans-3-hydroxy-L-proline degradation found in Azospirillum brasilense and degradation of the sugar acid L-lyxonate found in some bacteria. Other new pathways include degradation of the widespread pollutant 3,5,6-trichloro-2-pyridinol and the surfactant-derived compound 3-(4-sulfophenyl)butyrate.

In fungal metabolism we added the biosynthesis of lovastatin, one of the major cholesterol-lowering drugs that inhibits EC 1.1.1.34, hydroxymethylglutaryl-CoA reductase, the biosynthesis of ergothioneine, a histidine derivative that contains a thiol group and a trimethylated amine that is produced only by fungi, the degradation of glutathione in the yeast Saccharomyces cerevisiae, and an arginase-independent pathway for L-arginine degradation found in the yeast Kluyveromyces lactis.

Additional fungal pathways include the biosynthesis of the indole-diterpene aflatrem by Aspergillus flavus, the diterpenoid brassicicene C by the phytopathogen Alternaria brassicicola, the quinone compound atromentin that has anti-HIV properties, (-)-microperfuranone, which is found in terrestrial and marine fungi, and gliotoxin from the human pathogen Aspergillus fumigatus. Although gliotoxin appears to be a virulence factor, it has anticancer and antiviral properties. We also included a pathway for gliotoxin inactivation in this organism that prevents autointoxication. More additions include curated pathways for some fungal peptidyl alkaloid mycotoxins that have medicinal value, including the antitumor compound terrequinone A, the anticancer compounds fumitremorgin A, fumitremorgin C, and 5-N-acetylardeemin, the mycotoxic alkaloid acetylaszonalenin, the antibacterial and antifungal compound fumiquinazoline, the cholycystokinin inhibitor asperlicin E, and α-cyclopiazonate, a mycotoxin co-occurring with aflatoxin. We also added a detoxification pathway for α-cyclopiazonate in domesticated Aspergillus oryzae.

Animal Metabolism: We added a new variant of the methionine salvage cycle that operates in higher eukaryotes and involves polyamine biosynthesis, and a pathway for the synthesis of diphthamide, a unique posttranslationally modified histidine residue found only in the translation elongation factor 2 of archaea and eukaryotes. Other new animal pathways include mammalian variants of coenzyme A biosynthesis, and the degradation of L-asparagine and purine deoxyribonucleosides. We also curated pathways for the biosynthesis of fructose 2,6-bisphosphate, a potent metabolic regulator, and homocarnosine, a dipeptide found in mammalian brain and muscle that protects against oxidative stress and may be neuromodulatory. A pathway depicting the enzymes involved in the degradation of reactive oxygen species was also added.

Plant Metabolism: Two new plant secondary metabolite pathways involved in the biosynthesis of alkaloids were added to MetaCyc. Chelerythrine is a member of the benzylisoquinoline alkaloids that occur in four families of the order Ranunculales and has a broad range of antimicrobial, immunomodulatory and anticancer properties. The rare tetrahydroprotoberberine alkaloid R-canadine is found exclusively in the Papaveracae. It has been used in folk medicine and has therapeutic potential for dyspepsia.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of September 2014) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

Engineered Pathways:

We added an engineered pathway for the production of propane-1,2-diol (1,2-PDO) from lactate. 1,2-PDO is widely used in the production of unsaturated polyester resin and as a nontoxic replacement for ethylene glycol.

List of New and Updated Pathways

New Pathways

1,2-propanediol biosynthesis from lactate (engineered)

2-amino-3-hydroxycyclopent-2-enone biosynthesis

3-(4-sulfophenyl)butyrate degradation

3,5,6-trichloro-2-pyridinol degradation

5-N-acetylardeemin biosynthesis

6-hydroxymethyl-dihydropterin diphosphate biosynthesis III (Chlamydia)

α-cyclopiazonate biosynthesis

α-cyclopiazonate detoxification

acetylaszonalenin biosynthesis

aflatrem biosynthesis

arginine degradation XII

asperlicin E biosynthesis

atromentin biosynthesis

β-D-galactosaminyl-(1→3)-N-acetyl-α-D-galactosamine biosynthesis

brassicicene C biosynthesis

cardiolipin and phosphatidylethanolamine biosynthesis (Xanthomonas)

chelerythrine biosynthesis

CMP-N-acetyl-7-O-acetylneuraminate biosynthesis

dehydrodiconiferyl alcohol degradation

diphthamide biosynthesis (eukaryotes)

ergothioneine biosynthesis II (fungi)

flaviolin dimer and mompain biosynthesis

fumiquinazoline D biosynthesis

fumitremorgin A biosynthesis

fumitremorgin C biosynthesis

gliotoxin biosynthesis

gliotoxin inactivation

glutathione degradation (DUG pathway - yeast)

heme d₁ biosynthesis

heme biosynthesis III (from siroheme)

L-lyxonate degradation

lovastatin biosynthesis

mannojirimycin biosynthesis

methionine salvage cycle I (bacteria and plants)

methionine salvage cycle III (animals)

methylerythritol phosphate pathway II

methylthiolincosamide biosynthesis

mevalonate pathway III (archaea)

(-)-microperfuranone biosynthesis

prodigiosin biosynthesis

(R)-canadine biosynthesis

rhizocticin A and B biosynthesis

terrequinone A biosynthesis

trans-3-hydroxy-L-proline degradation

tyrosine degradation IV (to 4-methylphenol)

New Pathways from EcoCyc

D-lactate to cytochrome bo oxidase electron transport

glycerol-3-phosphate to cytochrome bo oxidase electron transfer

glycerol-3-phosphate to fumarate electron transfer

NADH to cytochrome bd oxidase electron transport II

NADH to cytochrome bo oxidase electron transfer II

pyruvate to cytochrome bd terminal oxidase electron transfer

pyruvate to cytochrome bo oxidase electron transfer

New Pathways from HumanCyc

asparagine degradation III (mammalian)

coenzyme A biosynthesis II (mammalian)

fructose 2,6-bisphosphate biosynthesis

homocarnosine biosynthesis

purine deoxyribonucleosides degradation

reactive oxygen species degradation (mammalian)

New Superpathways

superpathway of fumitremorgin biosynthesis

Updated Pathways

5-hydroxymethylfurfural degradation

α-amyrin biosynthesis

alkane oxidation

betulinate biosynthesis

C4 photosynthetic carbon assimilation cycle, NAD-ME type

C4 photosynthetic carbon assimilation cycle, NADP-ME type

C4 photosynthetic carbon assimilation cycle, PEPCK type

crocetin ester biosynthesis

D-serine degradation

Fe(II) oxidation

fumigaclavine biosynthesis

fusicoccin A biosynthesis

methionine salvage cycle II (plants)

nitrate reduction I (denitrification)

noscapine biosynthesis

oleanolate biosynthesis

ornithine lipid biosynthesis

reductive acetyl coenzyme A pathway

S-methyl-5-thio-α-D-ribose 1-phosphate degradation

siroheme biosynthesis

sophorolipid biosynthesis

tetrahydromethanopterin biosynthesis

tryptophan degradation II (via pyruvate)

ursolate biosynthesis

---

Release Notes for MetaCyc Version 18.1

MetaCyc KB Statistics

Pathways	2203
Reactions	11842
Enzymes	9878
Chemical Compounds	11432
Organisms	2552
Citations	41432

Released on June 23, 2014

New and Updated Pathways

We have added 56_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 22 pathways by adding commentary and updated enzyme and gene information, for a total of 78 new and updated pathways. Of the new pathways, 12 were contributed by HumanCyc curators. We also added one new superpathway.

Microbial Metabolism: In microbial metabolism we added pathways for the biosynthesis of the antibiotics elloramycin and tetracenomycin C, the lysophospholipase-inhibitor cyclooctatin, and the fungal metabolite paspaline, which is an intermediate in indole-diterpene biosynthesis. We also added pathways for the biosynthesis of the mycotoxins paxilline and patulin, the latter being a known food contaminant. In addition we curated a phosphatidylcholine biosynthesis pathway found in the plant pathogen Xanthomonas campestris and a pathway for an intermediate in Bacteroides fragilis capsular polysaccharide biosynthesis.

Other new pathways include the degradation of D-carnitine, gentisate, acetone, kojibiose, D-galactose, and the polythioesters 3,3'-thiodipropionate and 3,3'-dithiodipropionate, non-naturally occurring polymers containing sulfur in the thioester linkages of their backbone that can be synthesized by bacteria. We also added a novel meta-cleavage pathway for 2,3-dihydroxybenzoate, mineralization of the phenylurea herbicide linuron by strains of Variovorax, a fungal variant of choline degradation, and mannan degradation by mammalian gut and rumen symbionts.

We revised our existing pathway for the synthesis of mycolates, long fatty acids found in the cell walls of the Corynebacterineae taxon (a group of bacteria that includes the pathogen Mycobacterium tuberculosis), and updated several pathways related to sulfur metabolism, including the oxidation of sulfur, sulfite and thiosulfate and the reduction of sulfate. We also revised the pathway for the synthesis of the iron chelate pulcherrimin.

Animal Metabolism: We curated a unique pathway for threonine degradation in humans that differs from other mammals due to the fact that the threonine dehydrogenase gene present in other mammals is a pseudogene in humans. We also added an alternative lysine degradation pathway that is present in the adult mammalian brain. A new human biosynthetic pathway describes the generation of hydrogen sulfide, a compound that has anti-inflammatory properties, modulates blood pressure, and may also act as a neuronal messenger molecule. Another new pathway depicts the biosynthesis of carnosine, a dipeptide that may act as an anti-oxidant, a neuromodulator, a protective factor for diabetic neuropathy and a suppressor of cell senescence.

Plant Metabolism: In plant secondary metabolism we added many new pathways involved in the biosynthesis of flavonoids and phenylpropanoids, terpenoids, and lignans. These include unique acylation pathways for the biosynthesis of the blue pigment violdelphin and polyacylated cyanidin 3,7-diglucosides, a pathway for anthocyanin A11 which is the main and most complex anthocyanin in Arabidopsis, and one for the galloylated catechin units of proanthocyanidins which may have health-promoting effects in humans.

We added a biosynthetic pathway for the flavonol gossypetin, which has a specific tissue distribution that separates the flavonol aglycones in leaves from glucosylated flavonols in petals. We also added pathways for the biosynthesis of hydroxylated cinnamate conjugates including hydroxycinnamate sugar acid esters, and acetyl coutarate, which is the main hydroxycinnamate ester in spinach (Spinacia oleracea). From the ice plant Mesembryanthemum crystallinum we added a pathway involving a specific O-methyltransferase that catalyzes methylation in the meta-position of many phenylpropanoids with aromatic vicinal dihydroxy groups, contributing to their diversity in this plant.

We curated the biosynthesis of several triterpenoid avenacins (A-1, A-2, and derivatives) in oats (Avena sativa), which act as specific phytoalexins and allelopathic agents, as well as pathways for the acyl donors (N-methylanthraniloyl glucopyranose and benzoyl glucopyranose) that are used in avenacin A-1 and A-2 formation, respectively. In rice (Oryza sativa) we added pathways for the biosynthesis of key phytoalexin compounds such as the diterpenoids momilactone A, oryzalexins A-E, oryzalide A and phytocassane.

We also added a biosynthetic pathway for 3β-hydroxysesquiterpene lactones such as parthenolide, a potential anticancer and anti-inflammatory drug found in the medicinal plant feverfew (Tanacetum parthenium). New pathways for the glucosylation of the cytotoxic compounds secoisolariciresinol and podophyllotoxin provide insight into plant defense mechanisms against such compounds, which are valued as anti-cancer and antiviral drugs.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of May 2014) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

We are sad to say goodbye to Deepika Weerasinghe, a MetaCyc and HumanCyc curator, and thank her for her contribution, particularly in updating HumanCyc pathways and enzymes.

We would like to thank Dr. Ludovica Montanucci from Universitat Pompeu Fabra Barcelona for helping in the curation of HumanCyc and submitting several new human pathways to MetaCyc.

List of New and Updated Pathways

New Pathways

2,3-dihydroxybenzoate degradation

2-O-acetyl-3-O-trans-coutarate biosynthesis

3β-hydroxysesquiterpene lactone biosynthesis

3,3'-dithiodipropionate degradation

3,3'-thiodipropionate degradation

acetone degradation III (to propane-1,2-diol)

acylated cyanidin galactoside biosynthesis

anthocyanidin modification (Arabidopsis)

avenacin A-1 biosynthesis

avenacin A-2 biosynthesis

bactoprenyl-diphospho-acetamido-4-amino-6-deoxygalactopyranose biosynthesis

benzoyl-β-D-glucopyranose biosynthesis

choline degradation IV

cyanidin 3,7-diglucoside polyacylation biosynthesis

cyanidin dimalonylglucoside biosynthesis

cyclooctatin biosynthesis

D-carnitine degradation I

D-carnitine degradation II

D-galactose degradation V (Leloir pathway)

des-methyl avenacin A-1 biosynthesis

elloramycin biosynthesis

galloylated catechin biosynthesis

gentisate degradation II

gossypetin metabolism

hydroxycinnamate sugar acid ester biosynthesis

kojibiose degradation

linuron degradation

mannan degradation

momilactone A biosynthesis

N-methylanthraniloyl-β-D-glucopyranose biosynthesis

oryzalexin A, B, and C biosynthesis

oryzalexin D and E biosynthesis

oryzalide A biosynthesis

paspaline biosynthesis

patulin biosynthesis

paxilline and diprenylpaxilline biosynthesis

phenylpropanoids methylation (ice plant)

phosphatidylcholine biosynthesis VII

phytocassanes biosynthesis, shared reactions

podophyllotoxin glucosides metabolism

(+)-secoisolariciresinol diglucoside biosynthesis

sulfite oxidation V (SoeABC)

tetracenomycin C biosynthesis

violdelphin biosynthesis

New Pathways from HumanCyc

acyl carrier protein metabolism II

allopregnanolone biosynthesis

carnosine biosynthesis

GDP-glucose biosynthesis II

glycine betaine degradation II (mammalian)

hydrogen sulfide biosynthesis II (mammalian)

lysine degradation II (pipecolate pathway)

NAD phosphorylation and dephosphorylation II

pentose phosphate pathway (oxidative branch) II

phosphatidylserine biosynthesis I

phosphatidylserine biosynthesis II

threonine degradation V (Homo sapiens)

New Superpathways

superpathway avenacin A biosynthesis

Updated Pathways

artemisinin biosynthesis

avenacin biosynthesis, initial reactions

caffeine degradation V (bacteria, via trimethylurate)

cholate degradation (bacteria, anaerobic)

costunolide biosynthesis

diterpene phytoalexins precursors biosynthesis

galactose degradation IV

gentisate degradation I

L-carnitine degradation II

L-rhamnose degradation I

mycolate biosynthesis

pulcherrimin biosynthesis

salvigenin biosynthesis

sanguinarine and macarpine biosynthesis

sulfate reduction II (assimilatory)

sulfite oxidation I (sulfite oxidoreductase)

sulfur oxidation IV (intracellular sulfur)

taurine biosynthesis

tetrathionate reduction I (to thiosulfate)

thiosulfate oxidation III (multienzyme complex)

thiosulfate oxidation IV (multienzyme complex)

trimethylamine degradation

---

Release Notes for MetaCyc Version 18.0

MetaCyc KB Statistics

Pathways	2151
Reactions	11670
Enzymes	9699
Chemical Compounds	11226
Organisms	2515
Citations	40590

Released on March 24, 2014

New and Updated Pathways

We have added 73_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 44 pathways by adding commentary and updated enzyme and gene information, for a total of 117 new and updated pathways. Of the new pathways, one was contributed by an EcoCyc curator. We also added five new superpathways.

Microbial Metabolism: Among new pathways of interest are a novel arginine biosynthetic pathway that is found in the archaeon Sulfolobus acidocaldarius and biosynthetic pathways for the antibiotics tylosin and polymyxin A and the antimalarial drug FR-900098. Another pathway of interest is a chimeric superpathway that ties together biosynthetic routes for assorted dTDP-glucose-derived sugars that are used in various antibiotics produced by Actinobacteria. New bacterial degradation pathways include pathways for the catabolism of biogenic amines and the xenobiotic 2-chloroacrylate. Among updated pathways of note are the cyanobacterial pathway for plastoquinol biosynthesis and the so-called futalosine pathways - recently discovered pathways leading to menaquinone biosynthesis in a large number of bacteria, which were named after the pathway intermediate futalosine. Another revised pathway that should be mentioned is bacterial cholesterol degradation, a large and complex pathway that is believed to play an important role in the survival of the pathogen Mycobacterium tuberculosis in humans.

We also added many new yeast metabolic pathways involved in lipid and cofactor metabolism, including a pathway for the biosynthesis and incorporation of lipoate, an essential sulfur-containing cofactor of mitochondrial proteins, a mitochondrial pathway for the biosynthesis of the lipoate precursor octanoyl-acyl carrier protein, the remodeling pathway of phospholipids involved in the homeostasis of cell membrane glycerophospholipids, a pathway illustrating the metabolism of the monoacylglycerol precursors, and a sterol-steryl ester interconversion pathway that controls the amount of free sterols that can be incorporated into cell membranes. We also curated two pathways that depict the metabolism of thiamin triphosphate, a vitamin B1 derivative.

Animal Metabolism: We added mammalian variant pathways for NAD phosphorylation and dephosphorylation, the oxidative branch of the pentose phosphate pathway (a major source of reducing equivalents for biosynthetic reactions), and a pathway for acyl carrier protein metabolism that describes the conversion of inactive acyl carrier proteins to their active holo-form. We also curated a pathway for salvage of the important cofactor tetrahydrobiopterin In addition we updated several pathways including the GABA shunt that produces and conserves the supply of GABA, a primary pathway for L-lysine catabolism in mammals, the de novo biosynthesis of L-ornithine (a precursor of arginine in the urea and citrulline-nitric oxide cycles), and a mammalian variant of L-methionine salvage that provides S-adenosylmethionine, an important methyl donor for a number of pathways. Other new animal pathways describe mRNA capping and the formation of the most common cores of mucin-type glycoproteins. Other new pathways describe common modifications of terminal residues of O-glycans, and protein O-[N-acetyl]-glucosylation, a ubiquitous modification abundant on nuclear and cytoskeletal proteins of virtually all eukaryotes. Among invertebrates we added pathways for anaerobic energy metabolism, and insect sphingolipid, pheromone, and eye pigment biosynthesis.

Plant Metabolism: In plant primary metabolism we curated pathways for the biosynthesis of the vitamin E group of tocotrienols, and a cytosolic pathway for phenylalanine biosynthesis that significantly contributes to phenylalanine production in the cell and challenges the all-plastidal paradigm. In plant secondary metabolism we added a pathway for the biosynthesis of (4S)-carvone, a monoterpene with the characteristic odor of caraway and dill. We also curated the biosynthesis and degradation of the flavone luteolin triglucuronide, a tissue-specific metabolite that connects organogenesis and flavonoid metabolism in developing primary leaves of monocots. Updated plant pathways include a pathway for the biosynthesis of ginsenosides, a class of steroid glycosides found exclusively in ginseng, pathways for the biosynthesis of the sucrosyl oligosaccharides lychnose, isolychnose, mediose and stellariose (found in Stellaria media), and a pathway for secologanin and strictosidine biosynthesis.

Other Improvements

Engineered Pathways:

We added seven engineered pathways that describe the production of 1,3-propanediol, a precursor of the polyester poly(propylene terephtalate), in bacteria, the biosynthesis of β-carotene in rice (the so-called Golden Rice, which contains vitamin A as a result of this modification), production of the biofuels butanol and isobutanol in yeast starting with protein, bacterial production of plant coumarins and the flavonoid neringenin in bacteria, production of isoprene in bacteria, and the bacterial production of taxadiene, an intermediate in the biosynthesis of the anti-cancer drug taxol.

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of January 2014) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

Over the past year we have added 303 new EC entries, 112 of which during this release period. We also updated 367 EC entries during the last year, with 157 entries updated during this release.

In addition, we have set the directionality of more than 2000 reactions based on their EC classification. For example, reactions catalyzed by oxidases  were set  as physiologically unidirectional in the direction of hydrogen peroxide production, while transamination reactions were set to be reversible.

List of New and Updated Pathways

New Pathways

1,3-propanediol biosynthesis (engineered)

1,4-dihydroxy-6-naphthoate biosynthesis I

1,4-dihydroxy-6-naphthoate biosynthesis II

2-aminoethylphosphonate degradation III

2-chloroacrylate degradation I

2-chloroacrylate degradation II

(4S)-carvone biosynthesis

acyl carrier protein metabolism II

aminopropanol phosphate biosynthesis II

anaerobic energy metabolism (invertebrates, cytosol)

anaerobic energy metabolism (invertebrates, mitochondrial)

arginine biosynthesis IV (archaea)

aromatic biogenic amine degradation (bacteria)

arsenite oxidation II (respiratory)

aurachin A, B, C and D biosynthesis

aurachin RE biosynthesis

benzoate fermentation (to acetate and cyclohexane carboxylate)

β-carotene biosynthesis (engineered)

biotin biosynthesis from 8-amino-7-oxononanoate II

bombykol biosynthesis

butanol and isobutanol biosynthesis (engineered)

ceramide phosphoethanolamine biosynthesis

cob(II)yrinate a,c-diamide biosynthesis I (early cobalt insertion)

cob(II)yrinate a,c-diamide biosynthesis II (late cobalt incorporation)

coumarins biosynthesis (engineered)

crotonate fermentation (to acetate and cyclohexane carboxylate)

demethylmenaquinol-6 biosynthesis II

D-galactosamine and N-acetyl-D-galactosamine degradation

drosopterin and aurodrosopterin biosynthesis

dTDP-α-D-mycaminose biosynthesis

dTDP-β-L-4-epi-vancosamine biosynthesis

dTDP-β-L-evernitrose biosynthesis

dTDP-6-deoxy-α-D-allose biosynthesis

FR-900098 and FR-33289 antibiotics biosynthesis

hypotaurine degradation

indole degradation to anthranil and anthranilate

ipsdienol biosynthesis

isoprene biosynthesis II (engineered)

lipoate biosynthesis and incorporation (glycine cleavage system, yeast)

lipoate biosynthesis and incorporation (pyruvate dehydrogenase and oxoglutarate dehydrogenase, yeast)

luteolin triglucuronide biosynthesis

luteolin triglucuronide degradation

methylphosphonate degradation II

methymycin, neomethymycin and novamethymycin biosynthesis

monoacylglycerol metabolism (yeast)

mRNA capping I

mRNA capping II

mucin core 1 and core 2 O-glycosylation

mucin core 3 and core 4 O-glycosylation

mycinamicin biosynthesis

NAD phosphorylation and dephosphorylation II

narbomycin, pikromycin and novapikromycin biosynthesis

naringenin biosynthesis (engineered)

octanoyl-ACP biosynthesis (mitochondria, yeast)

pentose phosphate pathway (oxidative branch) II

phenylalanine biosynthesis (cytosolic, plants)

phospholipid remodeling (phosphatidate, yeast)

phospholipid remodeling (phosphatidylcholine, yeast)

phospholipid remodeling (phosphatidylethanolamine, yeast)

polymyxin A biosynthesis

protein O-[N-acetyl]-glucosylation

purine nucleotide salvage

sterol:steryl ester interconversion (yeast)

sulfoglycolysis

taxadiene biosynthesis (engineered)

terminal O-glycans residues modification

tetrahydrobiopterin salvage

tetramethylpyrazine degradation

thiamin triphosphate metabolism

tylosin biosynthesis

urate degradation to allantoin II

vitamin E biosynthesis (tocotrienols)

New Pathway from EcoCyc

5-(carboxymethoxy)uridine biosynthesis

New Superpathways

superpathway of anaerobic energy metabolism (invertebrates)

superpathway of demethylmenaquinol-6 biosynthesis II

superpathway of dTDP-glucose-derived antibiotic building blocks biosynthesis

superpathway of lipoate biosynthesis and incorporation (PDH, KGDH, GCV, yeast)

superpathway phosphatidate biosynthesis (yeast)

Updated Pathways

1,4-dihydroxy-6-naphthoate biosynthesis I

1,4-dihydroxy-6-naphthoate biosynthesis II

2-methylbutyrate biosynthesis

2-methylketone biosynthesis

5,6-dimethylbenzimidazole biosynthesis

adenosylcobalamin biosynthesis I (early cobalt insertion)

adenosylcobalamin biosynthesis II (late cobalt incorporation)

aminopropanol phosphate biosynthesis I

anhydromuropeptides recycling

aniline degradation

anthocyanin biosynthesis (cyanidin 3-O-glucoside)

cholesterol degradation to androstenedione II (cholesterol dehydrogenase)

citrate degradation

citrate lyase activation

Δ6-hexadecenoate biosynthesis

D-serine degradation

flavonoid biosynthesis

flavonol biosynthesis

formate reduction to 5,10-methylenetetrahydrofolate

GABA shunt

GDP-L-colitose biosynthesis

ginsenosides biosynthesis

hypusine biosynthesis

leucopelargonidin and leucocyanidin biosynthesis

L-serine degradation

luteolin glycosides biosynthesis

lychnose and isolychnose biosynthesis

lysine biosynthesis V

lysine degradation II

malonate decarboxylase activation

malonate degradation I (biotin-independent)

malonate degradation II (biotin-dependent)

methionine degradation II

methionine salvage II (mammalia)

methylphosphonate degradation I

nitroglycerin degradation

ornithine de novo biosynthesis

plastoquinol-9 biosynthesis II

secologanin and strictosidine biosynthesis

stellariose and mediose biosynthesis

superpathway of gibberellin biosynthesis

threonine degradation I

triacylglycerol biosynthesis

triacylglycerol degradation

---

Release Notes for MetaCyc Version 17.5

Released on October 11, 2013

MetaCyc KB Statistics

Pathways	2097
Reactions	11409
Enzymes	9148
Chemical Compounds	10965
Organisms	2460
Citations	37570

New and Updated Pathways

We have added 56_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 33 pathways by adding commentary and updated enzyme and gene information, for a total of 89 new and updated pathways. Of the new pathways, three were contributed by PMN (Plant Metabolic Network) curators and one was contributed by an EcoCyc curator. We also added eight new superpathways.

Microbial Metabolism: New biosynthetic pathways include L-cysteine in Mycobacterium tuberculosis, sucrose in methane and methanol-utilizing bacteria, dehydro-D-arabinono-1,4-lactone in fungi, and six pathways involved in the biosynthesis of aminocoumarin and anthracycline antibiotics in Streptomyces. We also added several nucleotide-activated sugar pathways including those involved in the bacterial biosynthesis of antibiotics, O-antigen and S-layer glycoproteins, and the prokaryotic and eukaryotic biosynthetic intermediates UDP-α-D-glucuronate, UDP-glucose, and UDP-D-galactose. In addition we curated pathways for the synthesis of post-transcriptionally modified nucleosides within tRNAs that are found in archaea and eukaryotes.

In microbial degradation we added pathways for acrylonitrile in bacteria, D-glucosaminate in Salmonella, and xylose and L-arabinose in archaea.

Fourteen new yeast primary metabolic pathways have also been added. Ten are involved in fatty acid and lipid metabolism including the peroxisomal β-oxidation of saturated fatty acids, degradation of activated unsaturated fatty acids, degradation of phosphatidylglycerol (involved in cardiolipin biosynthesis regulation), and re-synthesis of phosphatidylcholine. Four pathways are involved in the biosynthesis and salvage of thiamin (vitamin B1) and its phosphate derivatives, which are involved in many important aspects of cellular metabolism. They include biosynthesis of the thiamin pyrimidine moiety which differs in yeast from the animal and plant pathways, and thiamin salvage catalyzed by multifunctional enzymes.

Animal Metabolism: We added vertebrate steroid hormone biosynthetic pathways for progesterone and a variant of estradiol biosynthesis. Among invertebrates, new pathways depict ecdysteroid biosynthesis and metabolism in arthropods, synthesis of the biogenic amine octopamine, and an opine fermentation pathway found in marine invertebrates.

Plant Metabolism: In plant secondary metabolism, PMN curators added biosynthetic pathways for the flavonoids nevadensin and salvigenin that are found in basil and other plants, and the medicinal alkaloid papaverine found in the opium poppy. The two flavonoids have health benefits including a neuroprotective effect that has been attributed to salvigenin. Two superpathways for important alkaloid compounds, such as nicotine, were created to show how upstream rate-limiting reactions can affect the level of synthesis of the final product in the pathway.

Glycan Degradation Pathways: We have updated seven glycan degradation pathways with a new type of pathway diagram. The polymer structures are now shown using symbols for the glycan monomers. The location of sites cleaved by different enzymes is shown using color-coded arrows pointing to the bonds within the polymer structure that are cleaved (see for example xyloglucan degradation and chondroitin sulfate degradation). The new pathway diagrams were implemented in Pathway Tools which now supports the symbolic representation of glycans recommended by the Consortium for Functional Glycomics (CFG) using the Glyco-CT format for the import/export of such structures. We enabled curation of these glycan structures by developing a Pathway Tools interface for the GlycanBuilder software that was originally developed as the main interface for structure searches and results display in the EUROCarbDB databases. However, the introduction of the CFG symbolic representation of glycan structures has not replaced the existing atomic structures which can still be found for compounds in MetaCyc.

Other Improvements

Gibbs Free Energy:

Standard Gibbs free energy of formation (Δ_fG′°) values have been added to most MetaCyc compounds, and standard Gibbs free energy (Δ_rG′°) values have been added to most MetaCyc reactions. Some values were obtained from the experimental literature; most values were computed. The values were calculated for a pH of 7.3, which is the pH of an Escherichia coli cell, and the pH for which all compounds in MetaCyc are protonated. A total of 10,713 compounds and 10,186 reactions now have these Gibbs free energy values. The computation of estimated standard Δ_fG′° values for compounds and Δ_rG′° for reactions was performed using a technique published by Jankowski et al 2008 . The standard Gibbs free energy of reactions was computed using Gibbs free energy of formation values (Δ_fG′°) of the compounds involved in the reaction.

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of September 2013) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

List of New and Updated Pathways

New Pathways

3-amino-4,7-dihydroxy-coumarin biosynthesis

3-dimethylallyl-4-hydroxybenzoate biosynthesis

4-amino-2-methyl-5-phosphomethylpyrimidine biosynthesis (yeast)

4-methyl-5(β-hydroxyethyl)thiazole salvage (yeast)

7-(3-amino-3-carboxypropyl)-wyosine biosynthesis

9-cis, 11-trans-octadecadienoyl-CoA degradation (isomerase-dependent, yeast)

10-cis-heptadecenoyl-CoA degradation (yeast)

10-trans-heptadecenoyl-CoA degradation (MFE-dependent, yeast)

10-trans-heptadecenoyl-CoA degradation (reductase-dependent, yeast)

aclacinomycin biosynthesis

acrylonitrile degradation I

acrylonitrile degradation II

daunorubicin biosynthesis

dehydro-D-arabinono-1,4-lactone biosynthesis

D-glucosaminate degradation

doxorubicin biosynthesis

dTDP-β-L-noviose biosynthesis

dTDP-N-acetylthomosamine biosynthesis

dTDP-N-acetylviosamine biosynthesis

dTDP-3-acetamido-3,6-dideoxy-α-D-glucose biosynthesis

dTDP-D-β-fucofuranose biosynthesis

Escherichia coli serotype O86 O-antigen biosynthesis

ecdysone and 20-hydroxyecdysone biosynthesis

ecdysteroid metabolism (arthropods)

estradiol biosynthesis II

fatty acid β-oxidation (peroxisome, yeast)

L-arabinose degradation IV

L-cysteine biosynthesis V

methylwyosine biosynthesis

novobiocin biosynthesis

octopamine biosynthesis

oleate β-oxidation (isomerase-dependent, yeast)

oleate β-oxidation (reductase-dependent, yeast)

oleate β-oxidation (thioesterase-dependent, yeast)

phosphatidylcholine resynthesis via glycerophosphocholine

phosphatidylglycerol degradation

progesterone biosynthesis

pyruvate fermentation to opines

sucrose biosynthesis III

thiamin formation from pyrithiamine and oxythiamine (yeast)

thiamin salvage IV (yeast)

UDP-α-D-glucuronate biosynthesis (from UDP-glucose)

UDP-N-acetyl-α-D-fucosamine biosynthesis

UDP-N-acetyl-α-D-galactosaminuronate biosynthesis

UDP-N-acetyl-α-D-mannosaminouronate biosynthesis

UDP-N-acetyl-α-D-quinovosamine biosynthesis

UDP-N-acetyl-β-L-fucosamine biosynthesis

UDP-N-acetyl-β-L-quinovosamine biosynthesis

UDP-D-galactose biosynthesis

UDP-glucose biosynthesis

wybutosine biosynthesis

xylose degradation IV

New Pathways from Plant Metabolic Network (PMN)

nevadensin biosynthesis

papaverine biosynthesis

salvigenin biosynthesis  

New Pathway from EcoCyc

5-carboxymethyl ester uridine biosynthesis

Updated Glycan Degradation Pathways

(1,4)-β-xylan degradation

cellulose degradation I

chondroitin sulfate degradation

dermatan sulfate degradation

L-arabinan degradation

pectin degradation I

xyloglucan degradation I

New Superpathways

superpathway of anaerobic sucrose degradation

superpathway of dTDP-glucose-derived O-antigen building blocks biosynthesis

superpathway of GDP-mannose-derived O-antigen building blocks biosynthesis

superpathway of hyoscyamine and scopolamine biosynthesis

superpathway of nicotine biosynthesis

superpathway of steroid hormone biosynthesis

superpathway of UDP-N-acetylglucosamine-derived O-antigen building blocks biosynthesis

superpathway of UDP-glucose-derived O-antigen building blocks biosynthesis

Updated Pathways

2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis

26,27-dehydrozymosterol metabolism

base-degraded thiamin salvage

carbon disulfide oxidation I (anaerobic)

chlorophyllide a biosynthesis III (aerobic, light independent)

colanic acid building blocks biosynthesis

D-arabinose degradation II

D-sorbitol degradation I

dTDP-L-rhamnose biosynthesis I

galactose degradation III

ginsenoside degradation I

ginsenoside degradation II

glycine biosynthesis V

hypericin biosynthesis

indole-3-acetate degradation VIII (bacterial)

methionine salvage II (mammalia)

plant sterol biosynthesis

pyridoxal 5'-phosphate biosynthesis II

pyrrolysine biosynthesis

sucrose biosynthesis I (from photosynthesis)

sucrose degradation I (sucrose phosphotransferase)

sucrose degradation II (sucrose synthase)

sucrose degradation III (sucrose invertase)

superpathway of hexitol degradation (bacteria)

thiazole biosynthesis III (eukaryotic)

UDP-sugars interconversion

---

Release Notes for MetaCyc Version 17.1

Released on June 11, 2013

MetaCyc KB Statistics

Pathways	2042
Reactions	11111
Enzymes	8919
Chemical Compounds	10593
Organisms	2414
Citations	36329

New and Updated Pathways

We have added 50_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 29 pathways by adding commentary and updated enzyme and gene information, for a total of 79 new and updated pathways. Of the new pathways, four were contributed by PMN (Plant Metabolic Network) curators and two were contributed by a BsubCyc (the Bacillus subtilis PGDB) curator. We also added four new superpathways.

Microbial Metabolism: New bacterial biosynthetic pathways include pathways for the nonproteinogenic amino acids D-cycloserine and L-homophenylalanine, the secondary metabolite mycocyclosin, the pigment pulcherrimin, and a pathway describing the synthesis of iron-sulfur clusters. We also added a novel pathway for the biosynthesis of the antibiotic kanosamine, and a version of the TCA cycle found in acetogenic bacteria. New microbial catabolic pathways include several pathways for pectin and inositol degradation, as well as D-fructuronate and D-glucuronate degradation. We also reorganized our purine nucleotides biosynthesis and salvage pathways.

Animal Metabolism: We added new pathways describing mammalian sphingolipid biosynthesis and mammalian variants of glycolysis and gluconeogenesis. We also revised a pathway for the de novo biosynthesis of ceramides, lipid molecules that are found in high concentrations within the cell membrane and also act as second messengers that participate in cell differentiation, senescence and apoptosis. In addition we revised a pathway for the biosynthesis of serotonin and melatonin. These derivatives of L-tryptophan have a variety of important physiological functions including mood and sleep regulation.

Plant Metabolism: In plant primary metabolism we added pathways for the biosynthesis of coenzyme Q6, which is crucial for the function and maintenance of aerobic respiration in plants and yeast. Other pathways describe the mitochondrial and cytosolic interconversion of the major oxidized and reduced pyridine dinucleotides, which are involved in energy metabolism, electron transport, and the main metabolic cycles in plants and yeast.

In plant secondary metabolism we added new pathways involved in the biosynthesis and degradation of flavones, anthocyanins and alkaloids. Flavones and their derivatives exhibit pharmacological properties including antibacterial, antiviral and anticancer activities. Anthocyanins are the main pigments involved in the development of flower colors and color patterns, which play major roles in the reproductive biology of plants by attracting pollinators. The alkaloid lampranthin has high antioxidant and radical scavenging properties and is used as a food accessory.

PMN curators added a new sucrose biosynthesis pathway and revised pathways related to starch biosynthesis and degradation. These sugar metabolism and storage pathways are important to agricultural yields and biofuel production. Another new pathway describes how plants produce GA3, a growth-promoting gibberellin detected in many different plant species. A metabolic cluster was created to depict the biosynthesis of a number of structurally related pentacyclic triterpenoids. Enzymes with varying levels of specificity can produce this class of compounds, which are involved in plant defense and often have health-related applications.

Engineered Pathways: We added two engineered pathways that describe the production of 3-hydroxybutyrate, a precursor for the synthesis of plastics.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the Enzyme Commission (EC) definitions in MetaCyc with the latest information (as of May 2013) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) and the Joint Commission on Biochemical Nomenclature (JCBN), available from the ExplorEnz database.

List of New and Updated Pathways

New Pathways

[2Fe-2S] iron-sulfur cluster biosynthesis

adenosine deoxyribonucleotides de novo biosynthesis I

adenosine deoxyribonucleotides de novo biosynthesis II

adenosine ribonucleotides de novo biosynthesis

aerobic respiration (cytochrome c) (yeast)

anthocyanidin 3-malylglucoside biosynthesis (acyl-glucose dependent)

anthocyanin biosynthesis (pelargonidin 3-O-glucoside)

apigeninidin 5-O-glucoside biosynthesis

baicalein degradation (hydrogen peroxide detoxification)

baicalein metabolism

β-D-glucuronide and D-glucuronate degradation

cyanidin diglucoside biosynthesis (acyl-glucose dependent)

D-cycloserine biosynthesis

delphinidin diglucoside biosynthesis (acyl-glucose dependent)

D-fructuronate degradation

ergothioneine biosynthesis

gluconeogenesis III

glycolysis VI (mammalian)

guanosine deoxyribonucleotides de novo biosynthesis I

guanosine deoxyribonucleotides de novo biosynthesis II

guanosine ribonucleotides de novo biosynthesis

inosine-5'-phosphate biosynthesis III

lampranthin biosynthesis

L-homophenylalanine biosynthesis

luteolinidin 5-O-glucoside biosynthesis

mycocyclosin biosynthesis

myo-, chiro- and scillo-inositol degradation

myo-inositol degradation II

NAD/NADP-NADH/NADPH cytosolic interconversion (yeast)

NAD/NADP-NADH/NADPH mitochondrial interconversion (yeast)

pectin degradation I

pectin degradation II

pectin degradation III

pelargonidin diglucoside biosynthesis (acyl-glucose dependent)

photosynthetic 3-hydroxybutyrate biosynthesis

purine deoxyribonucleosides salvage

(R)- and (S)-3-hydroxybutyrate biosynthesis

rose anthocyanin biosynthesis II (via cyanidin 3-O-β-D-glucoside)

sphingolipid biosynthesis (mammals)

TCA cycle VII (acetate-producers)

ternatin C3 biosynthesis

ubiquinol-6 biosynthesis from 4-aminobenzoate (eukaryotic)

ubiquinol-6 bypass biosynthesis (eukaryotic)

wogonin metabolism

New Pathways from Plant Metabolic Network (PMN)

gibberellin biosynthesis V

pentacyclic triterpene biosynthesis

sucrose biosynthesis II

Yang cycle

New Pathway from BsubCyc

kanosamine biosynthesis II

pulcherrimin biosynthesis

New Superpathways

superpathway NAD/NADP - NADH/NADPH interconversion (yeast)

superpathway of adenosine nucleotides de novo biosynthesis I

superpathway of guanosine nucleotides de novo biosynthesis I

superpathway of ubiquinol-6 biosynthesis (eukaryotic)

Updated Pathways

4-hydroxyproline degradation I

4-hydroxyproline degradation II

adenosylcobalamin biosynthesis I (early cobalt insertion)

aerobic respiration (linear view)

anthocyanidin biosynthesis (cyanidin 3-O-glucosides)

archaetidylinositol biosynthesis

archaetidylserine and archaetidylethanolamine biosynthesis

CDP-archaeol biosynthesis

cis-vaccenate biosynthesis

ceramide de novo biosynthesis

coenzyme A biosynthesis

Entner-Doudoroff pathway II (non-phosphorylative)

Entner-Doudoroff pathway III (semi-phosphorylative)

gentiodelphin biosynthesis

hydroxylated fatty acid biosynthesis (plants)

kanamycin biosynthesis

ketogluconate metabolism

myo-inositol degradation I

nylon-6 oligomer degradation

phosphopantothenate biosynthesis I

proline degradation

putrescine biosynthesis III

sakuranetin biosynthesis

serotonin and melatonin biosynthesis

spermidine biosynthesis I

spermine biosynthesis

starch biosynthesis

starch degradation I

superpathway of β-D-glucuronide and D-glucuronate degradation

superpathway of purine nucleotides de novo biosynthesis I

ubiquinol-6 biosynthesis from 4-hydroxybenzoate

---

Release Notes for MetaCyc Version 17.0

Released on March 28, 2013

MetaCyc KB Statistics

Pathways	2000
Reactions	10924
Enzymes	8691
Chemical Compounds	10468
Organisms	2391
Citations	35063

New and Updated Pathways

We have added 84_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 31 pathways by adding commentary and updated enzyme and gene information, for a total of 115 new and updated pathways. Of the new pathways, 11 were contributed by PMN (Plant Metabolic Network) curators and two were contributed by an EcoCyc curator. Five of the pathways are bioenergy related.

Microbial Metabolism: New bacterial biosynthetic pathways describe the synthesis of the yellow carotenoid nostoxanthin, the yellow pigment grixazone, the activated sugar CDP-D-mannitol, the sialic acid N,N'-diacetyllegionaminate and a novel pathway for the synthesis of the biotin precursor 7-keto-8-aminopelargonate. New microbial catabolic pathways include a third variant of choline degradation, a fifth variant of nicotine degradation, a pathway for the degradation of the uncommon compounds L-glucose and L-gluconate, and a pathway for the degradation of S-methyl-5-thio-α-D-ribose 1-phosphate, a byproduct of polyamine synthesis that leads into isoprenoid biosynthesis. We also curated a cyanide detoxification pathway used by some fungal pathogens of cyanogenic plants.

We have expanded our coverage of sphingolipids, essential components of the plasma membrane in eukaryotic organisms, with pathways describing their biosynthesis, recycling and degradation in yeast. We also performed a thorough revision of our coverage of pyrimidine nucleotides metabolism, both prokaryotic and eukaryotic (see below).

Animal Metabolism: Several new and revised pathways describe the metabolism of pyrimidine nucleotides in mammalian cells, including the de novo biosynthesis of pyrimidine ribonucleotides and deoxyribonucleotides, their phosphorylation and dephosphorylation, the salvage and degradation of pyrimidine ribonucleosides and deoxyribonucleosides, and several superpathways.

Other new pathways describe the biosynthesis of resolvins and lipoxin, a series of antinflammatory mediators derived from omega-3 and omega-6 fatty acids. Other new pathways describe fatty acid β-oxidation in peroxisomes, and the degradation of phytol, a metabolite of chlorophyll.

Plant Metabolism: In plant secondary metabolism we added new pathways involved in the biosynthesis and degradation of flavonoids and their derivatives (flavonoid glycosides, methylated flavonoids, flavonoid acylglycosides, C-glycosylflavonoids), isoflavonoids and lignans. These compounds are involved in a number of plant biological processes such as defense, mycorrhizal symbioses, gametophyte fertility, UV-protection, hormone interactions and pollinator attraction. In humans, flavonoids have been shown to possess beneficial physiological properties and are of pharmacological and nutraceutical interest. We also revised a number of existing plant secondary metabolic pathways. In plant primary metabolism we added a new pathway for vitamin B6 salvage that illustrates the conversion of six vitamers to pyridoxal 5′-phosphate, which functions as an essential cofactor in numerous enzymatic activities.

PMN curators added new secondary metabolic pathways for the biosynthesis of the plant medicinal alkaloids noscapine, cephaeline and emetine and a new superpathway of scopolin and esculetin biosynthesis. In plant primary metabolism they added a new pathway for the biosynthesis of the unusual fatty acids pinolenic acid and coniferonic acid which contain bismethylene-interrupted double bonds, and a pathway for the biosynthesis of phytochromobilin, a heme-derived chromophore covalently bound to phytochromes. An alternative route for phenylalanine degradation found in lower plants was also curated.

PMN curators added several pathways from the model organism Chlamydomonas reinhardtii, a unicellular photosynthetic freshwater green alga. They include chlorophyllide a biosynthesis, chlorophyll a degradation, ergosterol biosynthesis (and its corresponding superpathway), and 7-dehydroporiferasterol biosynthesis. They also updated a fermentation superpathway found in this organism.

Bioenergy Pathways: Two new pathways replaced our existing pathway for the biosynthesis of linalool (an acyclic monoterpene alcohol) to accommodate the synthesis of different stereoisomers in different organisms. We also added a pathway for the degradation of β-myrcene that generates several monoterpenes that have potential as bioenergy products, and two bioenergy-related engineered pathways (see below).

Engineered Pathways: We added two pathways that describe ethylene production in different organisms, and a pathway for the synthesis of L-ascorbate.

Other Improvements

Social Media: We have now set up our own Twitter and Facebook accounts. To keep up with our latest news on BioCyc, please join us at

Facebook: https://www.facebook.com/BioCyc

Twitter: https://twitter.com/biocyc

Update of EC Reactions:

During this quarter we have updated the reactions in MetaCyc with the latest information (as of February 2013) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), available from the ExplorEnz database.

List of New and Updated Pathways

New Pathways

2'-deoxy-α-D-ribose 1-phosphate degradation

7-keto-8-aminopelargonate biosynthesis II

aspirin triggered resolvin D biosynthesis (17R series)

aspirin triggered resolvin E1 biosynthesis (18R series)

aspirin-triggered lipoxin biosynthesis

C20 prostanoid biosynthesis

CDP-D-mannitol biosynthesis

C-glycosylflavone biosynthesis II

C-glycosylflavone biosynthesis III

choline degradation III

CMP phosphorylation

CMP-legionaminate biosynthesis II

cyanide detoxification II

ethylene glycol biosynthesis

eupatolitin 3-O-glucoside biosynthesis

fatty acid β-oxidation VI (peroxisome)

flavonol acylglucoside biosynthesis I - kaempferol derivatives

flavonol acylglucoside biosynthesis II - isorhamnetin derivatives

flavonol acylglucoside biosynthesis III - quercetin derivatives

genistin gentiobioside biosynthesis

glucocorticoid biosynthesis

grixazone biosynthesis

kaempferide triglycoside biosynthesis

kaempferol diglycoside biosynthesis (pollen-specific)

kaempferol gentiobioside biosynthesis

L-ascorbate biosynthesis VI (engineered pathway)

L-glucose degradation

lipoxin biosynthesis

mineralocorticoid biosynthesis

myricetin gentiobioside biosynthesis

nicotine degradation V

nostoxanthin biosynthesis

phytol degradation

polymethylated kaempferol biosynthesis

polymethylated myricetin biosynthesis (tomato)

polymethylated quercetin biosynthesis

polymethylated quercetin glucoside biosynthesis I - quercetin series (Chrysosplenium)

polymethylated quercetin glucoside biosynthesis II - quercetagetin series (Chrysosplenium)

purine deoxyribonucleosides degradation

pyrimidine deoxyribonucleosides degradation

pyrimidine deoxyribonucleotide phosphorylation

pyrimidine deoxyribonucleotides de novo biosynthesis I

pyrimidine deoxyribonucleotides de novo biosynthesis II

pyrimidine deoxyribonucleotides de novo biosynthesis IV

pyrimidine deoxyribonucleotides biosynthesis from CTP

pyrimidine deoxyribonucleotides dephosphorylation

pyrimidine nucleobases salvage I

pyrimidine nucleobases salvage II

pyrimidine ribonucleosides salvage I

pyrimidine ribonucleosides salvage III

quercetin diglycoside biosynthesis (pollen-specific)

quercetin gentiotetraside biosynthesis

quercetin glucoside biosynthesis (Allium)

quercetin glucoside degradation (Allium)

quercetin triglucoside biosynthesis

resolvin D biosynthesis

rutin degradation (plants)

S-methyl-5-thio-α-D-ribose 1-phosphate degradation II

sesaminol glucoside biosynthesis

sphingolipid recycling and degradation (yeast)

stearate biosynthesis III (fungi)

threonine biosynthesis

UTP and CTP de novo biosynthesis

UTP and CTP dephosphorylation I

UTP and CTP dephosphorylation II

vitamin B6 salvage (plants)

New Pathways from Plant Metabolic Network (PMN)

7-dehydroporiferasterol biosynthesis

chlorophyll a degradation III

chlorophyllide a biosynthesis III

emetine biosynthesis

ergosterol biosynthesis II

esterified suberin biosynthesis

hyperxanthone E biosynthesis

noscapine biosynthesis

phenylalanine degradation V

phytochromobilin biosynthesis

pinolenic acid and coniferonic acid biosynthesis

New Bioenergy-Related Pathways

β myrcene degradation

ethylene biosynthesis IV

ethylene biosynthesis V

linalool biosynthesis I

linalool biosynthesis II

New Pathways from EcoCyc

cardiolipin biosynthesis III

muropeptide degradation

New Superpathways

superpathway of ergosterol biosynthesis II

superpathway of fermentation (Chlamydomonas reinhardtii)

superpathway of pyrimidine deoxyribonucleoside salvage

superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis

superpathway of pyrimidine nucleobases salvage

superpathway of pyrimidine ribonucleosides degradation

superpathway of pyrimidine ribonucleosides salvage

superpathway of scopolin and esculin biosynthesis

superpathway polymethylated quercetin/quercetagetin glucoside biosynthesis (Chrysosplenium)

Updated Pathways

(1'S,5'S)-averufin biosynthesis

7-keto-8-aminopelargonate biosynthesis III

acacetin biosynthesis

adenosine 5'-phosphoramidate biosynthesis

apigenin glycosides biosynthesis

camptothecin biosynthesis

cannabinoid biosynthesis

C-glycosylflavone biosynthesis I

curcumin glucoside biosynthesis

diphthamide biosynthesis

eumelanin biosynthesis

fatty acid α-oxidation II

fatty acid α-oxidation III

fatty acid beta oxidation II (peroxisome)

flavonol biosynthesis

isoflavonoid biosynthesis II

kaempferol glycoside bioysnthesis (Arabidopsis)

luteolin biosynthesis

luteolin glycosides biosynthesis

lysine degradation V

methylquercetin biosynthesis

pyrimidine deoxyribonucleosides salvage

pyrimidine deoxyribonucleotides de novo biosynthesis III

quercetin glycoside biosynthesis (Arabidopsis))

rutin biosynthesis

sophorolipid biosynthesis

sophorolipid degradation

sphingolipid biosynthesis (yeast)

superpathway of glycol metabolism and degradation

superpathway of pyrimidine ribonucleotides de novo biosynthesis

UMP biosynthesis

---

Release Notes for MetaCyc Version 16.5

Released on November 14, 2012

MetaCyc KB Statistics

Pathways	1928
Reactions	10481
Enzymes	8426
Chemical Compounds	10157
Organisms	2362
Citations	36796

New and Updated Pathways

We have added 60_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 29 pathways by adding commentary and updated enzyme and gene information, for a total of 89 new and updated pathways. Of the new pathways, 2 were contributed by PMN (Plant Metabolic Network) curators, one was contributed by EcoCyc curators, and one was submitted by MaizeGDB curators. Six of the pathways are bioenergy related.

Microbial Metabolism: New bacterial biosynthetic pathways include the synthesis of the antibiotic megalomicin A, the modified nucleotide sugar UDP-2,3-diacetamido-2,3-dideoxy-α-D-mannuronate (part of the O-antigen of Pseudomonas aeruginosa), cyanophycin (an amino acid polymer used by cyanobacteria to store nitrogen), the osmolyte N-acetylglutaminylglutamine amide, the terpenoid 2-methylisoborneol, the natural insecticide spinosyn A, and several hopanoids (a class of pentacyclic triterpenoids involved in membrane function, whose hopane skeletons are recognized as molecular fossils). We also increased our coverage of fungal metabolism by updating the biosynthetic pathways for the ergot alkaloids fumigaclavine C and ergotamine, both of which are known to cause ergotism in humans and animals. Other additions in microbial metabolism include new pathways for ammonia oxidation and denitrification by autotrophic ammonia oxidizers, resistance to the antibiotic triclosan (conferred by modified enoyl-[acyl-carrier-protein] reductases), salvage of fatty acids employed by the pathogen Pseudomonas aeruginosa, N-acetyl-D-galactosamine utilization by proteobacteria, and degradation of the xenobiotics 4-aminophenol and triethylamine.

Animal Metabolism: We curated a pathway for the detoxification of 4-hydroxy-2-nonenal, a highly reactive neurotoxic product of lipid peroxidation that is implicated in the pathogenesis and progression of Alzheimer's and Parkinson's diseases. Two new mammalian peroxisomal pathways for fatty acid α-oxidation were imported from HumanCyc.

Plant Metabolism: New pathways in plant primary metabolism include the biosynthesis of the plant hormones indole-3-acetate (IAA) and 5-deoxystrigol. New coverage in plant secondary metabolism focused on three classes of compounds - phenylpropanoids, widespread plants compounds that function in defense against phytopathogens and in stress response metabolism, terpenoids, many of which are of pharmacological interest due to their antibacterial, anti-inflammatory and cytotoxic activities that can aid in the fight against cancer, HIV and Alzheimer's disease, and cyanogenic glucosides, which provide plants with the means to efficiently repel herbivores and contribute to nitrogen assimilation and amino acid biosynthesis.
In phenylpropanoids we added pathways for the metabolism of daphnetin, daphnin, cichoriin, esculetin, geodin, asterrate, and furcatin. In terpenoids we added pathways for betulinate, ursolate, oleanolate, and steviol. In cyanogenic glucosides we added pathways for taxiphyllin, linustatin, neolinustatin, vicianin, and 3,4-dihydroxymandelonitrile β-D-glucose.
Other new pathways include the biosynthesis of glycyrrhetinate, which is used as sweetening and flavoring agents, the volatile scent precursors phenylethanol glycoconjugates, the volatile scent compounds phenylethyl acetate and 3,5-dimethoxytoluene, and the terpenophenolic compound olivetol.
PMN curators added two variants of the of the C4 photosynthetic carbon assimilation cycle that is found in plants with Kranz anatomy. Such plants can concentrate atmospheric CO₂ via C4 acids resulting in an increased efficiency of photosynthetic carbon fixation.

Bioenergy Pathways: Two new bacterial pathways describe the degradation of vanillin and vanillate, byproducts of lignin degradation. A new pathway for chitin degradation to ethanol and a new variant of docosahexanoate biosynthesis are relevant to the microbial synthesis of alternative energy compounds for biofuel production. We also updated existing pathways for microbial biosynthesis of the C10 monoterpenol linalool, the C10 monoterpenes pinene, 1,8-cineole and limonene, the C15 isoprenoid farnesene, and the long chain polyunsaturated fatty acids arachidonate and docosahexanoate.

Engineered Pathways: We curated engineered pathways for the biosynthesis of isobutanol and bisabolene, both potential sources of biofuel.

General Improvements

Atom Mappings in MetaCyc: Starting with version 16.5, atom mapping data is available for 8,281 MetaCyc reactions. An atom mapping describes for each atom of a reactant (excluding hydrogen) its corresponding atom in the product. Implicitly, an atom mapping illustrates which bonds are broken and created during the reaction. The atom mappings were computed using a technique described in Latendresse et al., Accurate atom-mapping computation for biochemical reactions, J. Chem. Inf. Model., September 2012. Atom mapping information is depicted in reactions by coloring conserved chemical moieties within a reaction (Firefox only). And if the user hovers the mouse over an atom in a reactant, that atom is highlighted in the product (Firefox only).

Glycan Structures:  Starting with version 16.5 of MetaCyc, glycan molecules may contain two types of structures: the atomic structure which is used for all chemical compounds, and a glycan structure that uses glycan monomers as the basic building blocks. Glycan structures are particularly useful for viewing and comprehending large polymeric glycans. Curation of the new structures was enabled by adding Pathway Tools support for the Glycan Builder software tool. For an example, see XXLG xyloglucan oligosaccharide.

New representation of EC Numbers in Pathway Tools: The Enzyme Commission (EC) classifies enzymes based on the reactions they catalyze. Since EC numbers are issued for enzymes and not reactions, a single EC number can be associated with multiple reactions, and on the other hand, a single reaction can be associated with multiple EC numbers. Until now, EC numbers were assigned in Pathway Tools to the reactions, with a limitation of only one EC number per reaction. Starting with version 16.5, EC numbers are represented by a new type of object within Pathway Tools PGDBs. For most reactions (those with just a single EC number) the main difference on the reaction page is that the EC number at the top of the page is now mouse-sensitive. Clicking on the EC number navigates to a new type of Pathway Tools page, the EC-number page. The difference is more obvious if a reaction is associated with multiple EC numbers. In these cases all of the EC numbers, along with their names, comments, citations, etc., appear on the reaction page. Similarly, visiting the page for an EC number that is associated with multiple reactions will enable the user to see all the reactions (and enzymes) that are associated with it. In addition, from now on, an enzyme will only be associated with an EC number if it is known to catalyze all of the official reactions (if there are more than one) associated with that EC number.

Other Improvements

CAZy links: CAZy is a database of carbohydrate-active enzymes that contain glycoside hydrolase, glycosyltransferase, polysaccharide lyase, carbohydrate esterase or carbohydrate-binding domains. These enzymes are classified into families that are given specific numbers (e.g. Glycoside Hydrolase Family 1). Relevant enzyme in MetaCyc now contain links to the CAZy page for their specific family. For an example, see CipA scaffoldin.

Update of EC Reactions:

During this quarter we have updated the reactions in MetaCyc with the latest information (as of september 2012) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), available from the ExplorEnz database.

We would like to thank Dr. Mary Schaeffer from MaizeGDB for submitting a new pathway for indole-3-acetate biosynthesis. We would like to thank David Damerell of Imperial College London and Rene Ranzinger of the University of Georgia for permitting us to use the Glycan Builder software and for helping in its integration.

List of New and Updated Pathways

New Pathways

2α,7β-dihydroxylation of taxusin

2-methylisoborneol biosynthesis

3,4-dihydroxymandelonitrile β-D-glucose biosynthesis

3,5-dimethoxytoluene biosynthesis

3-amino-3-phenylpropanoyl-CoA formation (Taxol 13C-side chain biosynthesis)

4-aminophenol degradation

4-hydroxy-2-nonenal detoxification

5-deoxystrigol biosynthesis

ammonia oxidation IV (autotrophic ammonia oxidizers)

asterrate biosynthesis

betulinate biosynthesis

cichoriin interconversion

cyanophycin metabolism

daphnetin modification

daphnin interconversion

dTDP-L-megosamine biosynthesis

eicosapentaenoate biosynthesis II (metazoa)

eicosapentaenoate biosynthesis IV (bacteria)

erythromycin A biosynthesis

erythromycin D biosynthesis

esculetin modification

fatty acid α-oxidation II

fatty acid α-oxidation III

fatty acid salvage

fumigaclavine biosynthesis

furcatin degradation

geodin biosynthesis

glycyrrhetinate biosynthesis

hopanoid biosynthesis (bacteria)

linustatin bioactivation

megalomicin A biosynthesis

N-acetyl-D-galactosamine degradation

N-acetylglutaminylglutamine amide biosynthesis

neolinustatin bioactivation

nitrifier denitrification

oleanolate biosynthesis

olivetol biosynthesis (olivetol synthase by-products synthesis)

phenylethanol glycoconjugate biosynthesis

phenylethyl acetate biosynthesis

spinosyn A biosynthesis

steviol biosynthesis

steviol glucoside biosynthesis (rebaudioside A biosynthesis)

taxiphyllin bioactivation

taxiphyllin biosynthesis

tea aroma glycosidic precursor bioactivation

triclosan resistance

triethylamine degradation

UDP-2,3-diacetamido-2,3-dideoxy-α-D-mannuronate biosynthesis

ursolate biosynthesis

vicianin bioactivation

New Pathways from Plant Metabolic Network (PMN)

C4 photosynthetic carbon assimilation cycle, NAD-ME type

C4 photosynthetic carbon assimilation cycle, PEPCK type

New Bioenergy-Related Pathways

bisabolene biosynthesis

chitin degradation to ethanol

docosahexanoate biosynthesis I

isobutanol biosynthesis

vanillin and vanillate degradation I

vanillin and vanillate degradation II

New Pathways from EcoCyc

proline to cytochrome bo oxidase electron transfer

New Pathways from MaizeGDB

indole-3-acetate biosynthesis I

New Superpathways

superpathway of megalomicin A biosynthesis

Updated Pathways

1,3,5-trimethoxybenzene biosynthesis

4-hydroxycoumarin and dicoumarol biosynthesis

alliin degradation

arachidonate biosynthesis

aurone biosynthesis

cannabinoid biosynthesis

chanoclavine I aldehyde biosynthesis

colchicine biosynthesis

γ-coniciene and coniin biosynthesis

cyanide detoxification I

docosahexanoate biosynthesis II

dTDP-L-rhamnose biosynthesis I

epoxypseudoisoeugenol-2-methylbutyrate biosynthesis

ergotamine biosynthesis

farnesene biosynthesis

fatty acid elongation -- saturated

geranyl acetate biosynthesis

germacrene biosynthesis

hyperforin and adhyperforin biosynthesis

indole-3-acetate biosynthesis II

linalool biosynthesis

monoterpene biosynthesis

patchoulol biosynthesis

phenylethanol biosynthesis

pyrethrin I biosynthesis

staphyloxanthin biosynthesis

superpathway of ergotamine biosynthesis

superpathway of indole-3-acetate conjugate biosynthesis

taxol biosynthesis

---

Release Notes for MetaCyc Version 16.1

Released on July 5, 2012

MetaCyc KB Statistics

Pathways	1877
Reactions	10247
Enzymes	8154
Chemical Compounds	9910
Organisms	2325
Citations	35021

New and Updated Pathways

We have added 59_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 22 pathways by adding commentary and updated enzyme and gene information, for a total of 81 new and updated pathways. Of the new pathways, four were contributed by PMN (Plant Metabolic Network) curators, one was contributed by EcoCyc curators and 10 are bioenergy related. We also added three new superpathways.

Microbial Metabolism: New microbial biosynthetic pathways include the antibiotics mithramycin, neomycin, kanamycin, paromomycin, ribostamycin, butirocin, and gentamycin, as well as multiple pathways describing the different mechanisms used by bacteria for the biosynthesis of alkanes and olefins. Two new pathways describing lipoate biosynthesis in Bacillus and lipoate salvage in Listeria were curated, along with a new tetrahydrobiopterin pathway found in cyanobacteria. In addition, we added biosynthetic pathways for the naturally occurring amino acid pyrrolysine, the caffeine metabolite theophylline, the pigment violacein, and for CDP-D-arabitol, a component of the Streptococcus capsular polysaccharide. We also added three pathways involved in bacterial protein glycosylation. In microbial degradation we added pathways for (-)-camphor, the isoflavone daidzein, nicotine, and L-1,2-propanediol. We also added pathways for mineralization of the aromatic ring-containing compounds 5-nitroanthranilate, 4-hydroxyacetophenone, 4-amino-3-hydroxybenzoate, 2-hydroxybiphenyl, 2,2'-dihydroxybiphenyl, 2-propylphenol, 2-isopropylphenol, and 4-coumarate.

We updated a number of existing pathways including the bacterial degradation of caffeine and nicotine, fungal galactose degradation, and two related pathways that are used by members of the family Chloroflexaceae for CO₂ fixation (the 3-hydroxypropionate cycle and a cycle for glyoxylate assimilation). A universal pathway that describes fatty acid β-oxidation was also updated.

In the bioenergy area we added bacterial pathways for the degradation of alginate and 1,5-anhydrofructose, and the conversion of glycerol to butanol, all of which are related to biofuel production. We also curated microbial pathways for the degradation of furfural and 5-hydroxymethylfurfural which are toxic byproducts of ethanol production. We updated existing pathways for the biosynthesis of the polyunsaturated fatty acid arachidonate and the methyl ketone 2-tridecanone. We also updated the pathway for botryococcenes and methylated squalene biosynthesis by the green alga Botryococcus braunii, a major hydrocarbon producer.

Animal Metabolism: We added two new pathways depicting the visual cycles used by molluscs and insects to regenerate the visual chromophores in their eyes, and a pathway employed by certain insects to generate the chromophore 11-cis-3-hydroxyretinal.  We also added a eukaryotic pathway for the biosynthesis of very-long-chain fatty acids by the microsomal elongase complex, and an insect pathway for chitin biosynthesis that is also found in other lower eukaryotes.

Plant Metabolism: We curated pathways for the biosynthesis of (+)-camphor and (-) camphor as well as a pathway for the biosynthesis of umbelliferone, a coumarin found in all higher plants that is an important intermediate in the synthesis of more complex derivatives. We also revised two pathways for the biosynthesis of nicotine and the plant hormone abscisic acid.

PMN curators added two malate-oxaloacetate shuttle pathways that transfer and balance reducing equivalents in the form of malate between organelles and the cytosol. They also curated a pathway showing the rapid, transient synthesis of the cellular signaling molecule phosphatidate and a minor shunt pathway for the biosynthesis of abscisic acid.

Engineered Pathways: We curated an engineered pathway for the biosynthesis of methyl ketones, which are potential biofuels. We also updated an engineered pathway for long-chain fatty acid ester biosynthesis for microdiesel production.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the reactions in MetaCyc with the latest information (as of May 2012) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), available from the ExplorEnz database.

List of New and Updated Pathways

New Pathways

(+)-camphor biosynthesis

(-)-camphor biosynthesis

(-)-camphor degradation

11-cis-3-hydroxyretinal biosynthesis

2,2'-dihydroxybiphenyl degradation

2-hydroxybiphenyl degradation

2-isopropylphenol degradation

2-propylphenol degradation

4-amino-3-hydroxybenzoate degradation

4-hydroxyacetophenone degradation

4-coumarate degradation (anaerobic)

5-nitroanthranilate degradation

brassinosteroids inactivation

butirosin biosynthesis

CDP-D-arabitol biosynthesis

chitin biosynthesis

daidzin and daidzein degradation

docosahexanoate biosynthesis

eicosapentaenoate biosynthesis from arachidonate

gentamicin biosynthesis

hentriaconta-3,6,9,12,15,19,22,25,28-nonaene biosynthesis

kanamycin biosynthesis

L-1,2-propanediol degradation

lipoate biosynthesis and incorporation III (Bacillus)

lipoate salvage II

mithramycin biosynthesis

neomycin biosynthesis

nicotine degradation II

paromamine biosynthesis I

paromamine biosynthesis II

paromomycin biosynthesis

pyrrolysine biosynthesis

ribostamycin biosynthesis

tetrahydrobiopterin biosynthesis III

the visual cycle (insects)

the visual cycle II (molluscs)

theophylline degradation

UDP-N,N'-diacetylbacillosamine biosynthesis

umbelliferone biosynthesis

undecaprenyl diphosphate-linked heptasaccharide biosynthesis

undecaprenyl-diphosphate-linked di- and trisaccharide biosynthesis

very long chain fatty acid biosynthesis II

violacein biosynthesis

(Z)-9-tricosene biosynthesis

New Pathways from Plant Metabolic Network (PMN)

abscisic acid biosynthesis shunt

malate-oxaloacetate shuttle I

malate-oxaloacetate shuttle II

phosphatidate metabolism, as a signaling molecule

New Bioenergy-Related Pathways

1,5-anhydrofructose degradation

5-hydroxymethylfurfural degradation

alginate degradation

alkane biosynthesis I

alkane biosynthesis II

furfural degradation

glycerol degradation to butanol

methyl ketone biosynthesis

terminal olefins biosynthesis I

terminal olefins biosynthesis II

New Pathways from EcoCyc

D-serine degradation

New Superpathways

superpathway of butirocin biosynthesis

superpathway of neomycin biosynthesis

superpathway of the 3-hydroxypropionate cycle

Updated Pathways

2-oxopentenoate degradation

2-tridecanone biosynthesis

3-hydroxypropionate cycle

4-aminobenzoate biosynthesis

abscisic acid biosynthesis

arachidonate biosynthesis

botryococcenes and methylated squalene biosynthesis

brassinosteroids inactivation

caffeine degradation III

caffeine degradation IV

caffeine degradation V

chorismate biosynthesis from 3-dehydroquinate

cinnamate and 3-hydroxycinnamate degradation to 2-oxopent-4-enoate

fatty acid β-oxidation I

galactose degradation IV

glyoxylate assimilation

nicotine biosynthesis

long chain fatty acid ester synthesis for microdiesel production

nicotine degradation I

spermidine biosynthesis II

trehalose biosynthesis I

trehalose degradation II (trehalase)

---

Release Notes for MetaCyc Version 16.0

Released on February 17, 2012

MetaCyc KB Statistics

Pathways	1842
Reactions	10262
Enzymes	7893
Chemical Compounds	9622
Organisms	2263
Citations	33541

New and Updated Pathways

We have added 75_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 10 pathways by adding commentary and updated enzyme and gene information, for a total of 85 new and updated pathways. Of the new pathways, 13 were contributed by PMN (Plant Metabolic Network) curators, three were contributed by EcoCyc curators and four are bioenergy related. We also added 8 new superpathways and updated 5 existing ones.

Microbial Metabolism: New microbial biosynthetic pathways include the antibiotics oleandomycin, erythromycin, lincomycin, pentalenolactone and the related neopentalenoketolactone, as well as pathways leading to the synthesis of the unusual deoxysugars that are often attached to macrolide antibiotics, including D-desosamine, L-mycarose, L-olivose, D-olivose, D-oliose and D-mycarose. A topic that received special attention is thiamin biosynthesis, where we reconstructed our existing pathways, defined different pathways for Escherichia coli, Bacillus subtilis, and eukaryotic organisms, and created several salvage pathways. Additional biosynthetic pathways include dTDP-3-acetamido-3,6-dideoxy-α-D-galactose (a deoxysugar found in the S-layer of the bacterium Aneurinibacillus thermoaerophilus), and a partial plastoquinol pathway from cyanobacteria.

In bacterial degradation we added pathways for several sterols, including two emerging bacterial pathways for the degradation of cholesterol, one for testosterone and androsterone, and one less-well characterized pathway for the plant-derived sitosterol. We also added new pathways for the degradation of methylamine, trimethylamine, styrene, ricinine (an alkaloid produced by the castor oil plant) and chitin, an important nutrient in the ocean. In addition, we significantly improved our coverage of L-ascorbate (vitamin C) degradation by creating three new pathways and revising the two already present.

Other new pathways describe the GS/GOGAT ammonium assimilation pathways (one from plants, fungi, and diatoms and the other from non-photosynthetic bacteria and archaea), and a TCA cycle variant for mycobacteria.

Updated microbial pathways include methanogenesis from acetate, the cycles of several 2-oxo acid dehydrogenases, such as the pyruvate dehydrogenase complex, and several variants of the TCA cycles.

In the bioenergy area we added engineered pathways for the biosynthesis of isopropanol and butanol in Escherichia coli utilizing enzymes from Clostridia and the phototrophic protist Euglena gracilis. We also added an engineered pathway for the autotrophic biosynthesis of butanol in a cyanobacterium, which involves the conversion of fixed carbon dioxide into butanol. Another new pathway describes xylose degradation by the thermophilic bacterium Bacillus coagulans, which can catalyze this conversion at pH 5.0 and elevated temperature of 60, making it a promising candidate for the production of ethanol from lignocellulosic biomass.

Animal Metabolism: A new pathway describes the repair of a non-active form of NADH, known as NADHX, which is formed as a side product of the enzyme glyceraldehyde-3-phosphate dehydrogenase. We have also updated the molybdenum cofactor (MoCo) and the thiamin biosynthesis pathways to reflect recent findings.

Plant Metabolism: In plant metabolism we have completely redefined the pathways for benzoxazinoid glucosides biosynthesis (DIBOA, DIMBOA and HMDBOA). We also added pathways for the biosynthesis of methylbutenol, a volatile secondary metabolite produced by Pinus species, epoxy fatty acids found in oat seeds, and an Allium-derived lachrymator.

PMN curators have also added a number of new pathways. Four of them relate to the uptake and metabolism of selenate, a process that has important ramifications for human nutrition and the phytoremediation of toxic soils. These pathways have also been used to generate a revised superpathway of Se-compound metabolism. Protection from another type of potentially toxic compound, phenolics, has been described in the phenolic malonylglucosides metabolism pathway. Plants may also produce compounds that are intended to be toxic to plant predators such as fungi and herbivorous insects. Biosynthetic pathways for three such defense compounds are described for the diterpenoid compounds kauralexin and zealexin and the non-standard amino acid L-N^δ-acetylornithine. An alternative pathway for the degradation of chlorophyll a, an important photosynthetic pigment compound, has also been added. Other additions include biosynthetic pathways for the antibacterial plant prenylflavonoid compound sophoraflavanone G, and the economically important natural insecticide pyrethrin, which is found in the seed cases of chrysanthemums.

Engineered Pathways: In this category we added a recombinant pathway constructed with plant and yeast enzymes that can produce analogs of gingerol in E. coli. Gingerol derivatives are plant natural products known to have beneficial effects on human health. Several additional engineered pathways are described in the bioenergy section above.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the reactions in MetaCyc with the latest information (as of January 2012) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by incorporating the current version of supplement 17. We also updated names and synonyms for enzymes with full EC numbers by incorporating this data from the ExplorEnz database.

List of New and Updated Pathways

New Pathways

4-amino-2-methyl-5-diphosphomethylpyrimidine biosynthesis

acetyl-CoA biosynthesis II (NADP-dependent pyruvate dehydrogenase)

ammonia assimilation cycle I

ammonia assimilation cycle II

androstenedione degradation

base-degraded thiamin salvage

chitin degradation II

chitin derivatives degradation

cholesterol degradation to androstenedione I (cholesterol oxidase)

cholesterol degradation to androstenedione II (cholesterol dehydrogenase)

DIBOA-glucoside biosynthesis

DIMBOA-glucoside biosynthesis

dTDP-3-acetamido-3,6-dideoxy-α-D-galactose biosynthesis

dTDP-D-desosamine biosynthesis

dTDP-D-olivose, dTDP-D-oliose and dTDP-D-mycarose biosynthesis

dTDP-L-mycarose biosynthesis

dTDP-L-olivose biosynthesis

eicosapentaenoate biosynthesis

epoxy fatty acid biosynthesis

erythromycin biosynthesis

glycerophosphodiester degradation

hydroxymethylpyrimidine salvage

L-ascorbate degradation II (bacterial, aerobic)

L-ascorbate degradation III

L-ascorbate degradation V

lincomycin biosynthesis

mandelate degradation to acetyl-CoA

methanol oxidation to formaldehyde I

methylamine degradation I

methylamine degradation II

methylbutenol biosynthesis

NADH repair

naphthalene degradation to acetyl-CoA

nectroscordum lachrymator biosynthesis

neopentalenoketolactone and pentalenate biosynthesis

oleandomycin activation/inactivation

oleandomycin biosynthesis

pentalenolactone biosynthesis

plastoquinol-9 biosynthesis II

ricinine degradation

sitosterol degradation to androstenedione

styrene degradation

TCA cycle V (2-oxoglutarate:ferredoxin oxidoreductase)

testosterone and androsterone degradation to androstendione

thiamin diphosphate biosynthesis I (E. coli)

thiamin diphosphate biosynthesis II (Bacillus)

thiamin diphosphate biosynthesis III (Staphylococcus)

thiamin diphosphate biosynthesis IV (eukaryotes)

thiamin salvage I

thiamin salvage II

thiamin salvage III

thiazole biosynthesis I (E. coli)

thiazole biosynthesis II (Bacillus)

thiazole biosynthesis III (eukaryotes)

trimethylamine degradation

New Pathways from Plant Metabolic Network (PMN)

6-gingerol analog biosynthesis

chlorophyll a degradation II

kauralexin biosynthesis

L-N^δ-acetylornithine biosynthesis

phenolic malonylglucosides biosynthesis

pyrethrin I biosynthesis

selenate reduction

seleno-amino acid biosynthesis

seleno-amino acid detoxification and volatilization I

seleno-amino acid detoxification and volatilization II

seleno-amino acid detoxification and volatilization III

sophoraflavanone G biosynthesis

zealexin biosynthesis

New Bioenergy-Related Pathways

1-butanol autotrophic biosynthesis

isopropanol biosynthesis

pyruvate fermentation to butanol II

xylose degradation IV

New Pathways from EcoCyc

D-serine degradation

hydrogen sulfide biosynthesis

methylphosphonate degradation

New Superpathways

superpathway of aromatic compound degradation via 2-oxopent-4-enoate

superpathway of cholesterol degradation I (cholesterol oxidase)

superpathway of cholesterol degradation II (cholesterol dehydrogenase)

superpathway of erythromycin biosynthesis

superpathway of guanine and guanosine salvage

superpathway of testosterone and androsterone degradation

superpathway of thiamin diphosphate biosynthesis II

superpathway of trimethylamine degradation

Updated Pathways

acetyl-CoA biosynthesis I (pyruvate dehydrogenase complex)

arachidonate biosynthesis

glycerol degradation I

L-ascorbate degradation I (bacterial, anaerobic)

L-ascorbate degradation IV

methanogenesis from acetate

molybdenum cofactor biosynthesis

TCA cycle I (prokaryotic)

TCA cycle IV (2-oxoglutarate decarboxylase)

UDP-N-acetyl-D-galactosamine biosynthesis II

Updated Superpathways

superpathway of ammonia assimilation (plants)

superpathway of benzoxazinoid glucosides biosynthesis

superpathway of seleno-compound metabolism

superpathway of thiamin diphosphate biosynthesis I

superpathway of thiamin diphosphate biosynthesis III (eukaryotes)

 

---

Release Notes for MetaCyc Version 15.5

Released on October 21, 2011

MetaCyc KB Statistics

Pathways	1790
Reactions	9609
Enzymes	7611
Chemical Compounds	9277
Organisms	2216
Citations	31145

New and Updated Pathways

We have added 43_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised seven pathways by adding commentary and updated enzyme and gene information, for a total of 50 new and updated pathways. Of the new pathways, four were contributed by PMN (Plant Metabolic Network) curators, and four are bioenergy related. We also added one new superpathway.

Microbial Metabolism: New biosynthetic pathways include two variants for the production of the plant hormone ethylene by microorganisms that live in association with plants, pathways for the activated form of forosamine, an unusual deoxygenated sugar found in several natural products, ornithine lipids, which are amino acid-containing acyl-oxyacyl lipids found in some bacteria, and bacterial pyrrolnitrin, a secondary product with antibacterial and antifungal activity. We added a new spermidine biosynthetic pathway found in thermophilic prokaryotes, two additional variants of phosphatidylcholine biosynthesis, and a 2-aminoethylphosphonate biosynthetic pathway studied in Tetrahymena pyriformis. We have revised our coverage of molybdenum cofactor (MoCo) biosynthesis to reflect recent knowledge, and created eukaryotic and prokaryotic variants of the pathway.

In the area of polymer degradation we added pathways describing the degradation of the polymers agarose, ι-carrageenan, κ-carrageenan, λ-carrageenan and porphyran, all of which are produced by red algae; gellan, a polymer produced by the bacterium Sphingomonas elodea; and a unique catabolic pathway for chitin characterized from a hyperthermophilic archaeon. We also added a fungal rutin (a plant secondary metabolite) catabolic pathway and a second pathway for 2-aminoethylphosphonate degradation.

In the bioenergy area we added two more pathways for cellulosic biomass degradation, describing the degradation of xyloglucan and glucuronoarabinoxylan, both important components of hemicellulose. We also revised a pathway that describes xyloglucan biosynthesis.

Animal Metabolism: We added several pathways describing the metabolism of retinoid compounds, also known as vitamin A. These pathways describe the synthesis of all-trans-retinol from dietary inputs, its conversion to all-trans-retinoate, the active form of vitamin A in many tissues, and the visual cycle that takes place in the retinal pigment epithelium (RPE). In the RPE all-trans-retinol is converted to 11-cis-retinol and incorporated into rhodopsin, where it reverts back to the trans form upon absorption of a photon.  We also curated pathways for the biosynthesis of senecionine-N-oxide which is used by lepidopteran insects to detoxify the plant pyrrolizidine alkaloid senecionine.

Plant Metabolism:  In plant primary metabolism we curated pathways for biosynthesis of the important signal molecule nitric oxide, the phytochelatin isoform homophytochelatin and its precursor homoglutathione, and a di-isomerase-dependent alternative degradation route for fatty acids with cis-double bonds on odd-number carbons (e.g. oleate). In plant secondary metabolite biosynthesis we curated pathways for the phenylpropanoid 6-gingerol, a flavor component of raw ginger;  the lignans justicidin B and diphyllin, which are of pharmaceutical interest; neoxanthin, a precursor of the hormone abscisic acid; and a second pathway for the sesquiterpenoid santalene. We also curated steps in the pathway used by carnivorous plants for the degradation of insect chitin, and a plant pathway for glutathione-mediated detoxification.

Engineered Pathways: This is the first release of MetaCyc that incorporates metabolically engineered pathways. Our first engineered pathways describe the production of hydrogen and hexanol, and the synthesis of long chain fatty acid esters for biodiesel production. The titles of engineered pathways are clearly marked as such, and a note above the commentary section informs users about the differences between natural and engineered pathways in MetaCyc.

Other Improvements

Increased Database Links to PubChem and KEGG

We have added extensive links from MetaCyc to PubChem and to KEGG. MetaCyc reactions now contain links to 4,014 KEGG reactions. MetaCyc compounds now contain 4,449 links to KEGG compounds and 8,814 links to PubChem compounds.

Update of EC Reactions:

During this quarter we have updated the reactions in MetaCyc with the latest information (as of May 2011) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by incorporating the current version of supplement 17. We also updated names and synonyms for enzymes with full EC numbers by incorporating this data from the ExplorEnz database.

List of New and Updated Pathways

New Pathways

2-aminoethylphosphonate biosynthesis

2-aminoethylphosphonate degradation II

3-methylbutanol biosynthesis

6-gingerol biosynthesis

acidification and chitin degradation (in carnivorous plants)

agarose degradation

chitin degradation (archaea)

diphyllin biosynthesis

dTDP-D-forosamine biosynthesis

ethylene biosynthesis II (microbes)

ethylene biosynthesis III (microbes)

gellan degradation

ι-carrageenan degradation

justicidin B biosynthesis

κ-carrageenan degradation

λ-carrageenan degradation

linezolid resistance

molybdenum cofactor biosynthesis II (eukaryotes)

neoxanthin biosnythesis

nitric oxide biosynthesis I (in plants)

ornithine lipid biosynthesis

phosphatidylcholine biosynthesis V

phosphatidylcholine biosynthesis VI

porphyran degradation

pyrrolnitrin biosynthesis

pyruvate fermentation to hexanol

retinoate biosynthesis I

retinoate biosynthesis II

retinol biosynthesis

rutin degradation

santalene biosynthesis II

senecionine N-oxide biosynthesis

spermidine biosynthesis III

tRNA methylation (yeast)

the visual cycle

New Pathways from Plant Metabolic Network (PMN)

fatty acid beta-oxidation V (unsaturated, odd number, di-isomerase-dependent)

glutathione-mediated detoxification II

homoglutathione biosynthesis

homophytochelatin biosynthesis

New Bioenergy-Related Pathways

glucuronoarabinoxylan degradation

long chain fatty acid ester synthesis for microdiesel production

trans, trans-farnesol biosynthesis

xyloglucan degradation III (cellobiohydrolase)

New Superpathways

superpathway of methanogenesis

Updated Pathways

bergamotene biosynthesis I

bergamotene biosynthesis II

molybdenum cofactor biosynthesis I (prokaryotes)

methylthiopropionate degradation I (cleavage)

phosphatidylcholine biosynthesis I

phosphonoacetate degradation

Updated Bioenergy-Related Pathways

xyloglucan biosynthesis

---

Release Notes for MetaCyc Version 15.1

Released on June 8, 2011

MetaCyc KB Statistics

Pathways	1747
Reactions	9460
Enzymes	7424
Chemical Compounds	9199
Organisms	2170
Citations	29927

New and Updated Pathways

We have added 71_{[more info]} new pathways to MetaCyc since the last release. In addition, we significantly revised 12 pathways by adding commentary and updated enzyme and gene information, for a total of 83 new and updated pathways.  Of the new pathways, 13 were contributed by PMN (Plant Metabolic Network) curators. We also added 2 new superpathways and updated one superpathway.

Microbial Metabolism: New microbial biosynthetic pathways include the 7-deazapurine antibiotics toyocamycin and sangivamycin, the macrolide antibiotic candicidin (a potent anti-fungal agent), the symmetrical C30 carotenoid 4,4'-diapolycopenedioate, the betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine, the activated sialic acid-like nonulosonate derivative CMP-legionaminate, which is involved in the synthesis of virulence-associated cell surface glycoconjugates, and a new pathway for demethylmenaquinol-8 that operates in the pathogens Helicobacter pylori and Campylobacter jejuni.

New degradation pathways focus primarily on the degradation of polymers that make up plant biomass. We added pathways for the degradation of cellulose, rhamnogalacturonan type I, (1,3)-β-D-xylan, (1,4)-β-D-xylan, L-arabinan, and xyloglucan. We also added two L-rhamnose degradation pathways that involve non-phosphorylated intermediates. In addition, we added a pathway for the degradation of sulfoacetaldehyde, three pathways (for microbes, protozoa, and mammals) for the degradation of S-methyl-5'-thioadenosine, an intermediate of methionine salvage, and a pathway for the degradation of chlorogenic acid.

We have significantly expanded our coverage of hydrogen production by adding seven pathways describing the process in different organisms and by different types of hydrogenases.

In archaeal metabolism we added the methylaspartate cycle, a pathway used by many halobacteria to generate biosynthetic precursor metabolites from acetyl-CoA, a pathway for the biosynthesis of archaeosine, a modified nucleoside found in the majority of archaeal tRNAs, and a pathway for the synthesis of 6-hydroxymethyl-dihydropterin diphosphate, a precursor of several important cofactors including tetrahydrofolate, methanopterin and sarcinapterin. We also added three archaeal pathways for the extracellular and intracellular degradation of starch and a pathway for oxidative xylose degradation

Animal Metabolism: We added four vertebrate hormone biosynthetic pathways from HumanCyc. They describe the biosynthesis of leukotrienes, the steroid hormone precursor pregnenolone, and the androgen and estrogen steroid hormones.

Plant Metabolism: New pathways in plant secondary metabolite biosynthesis describe the synthesis of scopoletin, a plant defense compound with many pharmacological effects, sporopollenin, which constitutes the outer layer of spores and the pollen wall, salidroside, a pharmaceutically important metabolite, sulfur volatiles involved in the plant defense response, methylhalides, salicin and salicortin, which are phenolic glycoside defense compounds found in Populus and Salix species, salicylate glucosides, which are plant defense compounds, specific volatile esters that contribute to fruit flavors, o-diquinones, which are involved in fruit browning, and the recently characterized flavonoid biosynthesis pathway in Equisetum.

We also added pathways describing the oxidative cleavage of C-C double bonds in carotenoids by carotenoid cleavage dioxygenases and a pathway for cyanide detoxification during fruit ripening.

In plant primary metabolism we added new pathways for the synthesis of fatty acids in plant mitochondria, the enrichment of polyunsaturated fatty acids in oil seeds, the synthesis of polyhydroxy fatty acids from linoleate and linolenate, the synthesis of the cyclic sugar alcohol pinitol, the synthesis of the uncommon nucleoside adenosine 5'-phosphoramidate, and the synthesis of the sugars laminaribiose and callose. We also added a new starch degradation pathway that shows the activity of kinases and phosphatases in the early stages of starch granule degradation in chloroplasts, and a pathway that describes two enzymatic mechanisms for detoxifying reactive carbonyl compounds formed by fatty acid lipid peroxidation in chloroplasts.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the reactions in MetaCyc with the latest information (as of May 2011) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by incorporating the current version of supplement 17. We also updated names and synonyms for enzymes with full EC numbers by incorporating this data from the ExplorEnz database.

List of New and Updated Pathways

New Pathways

4,4'-diapolycopenedioate biosynthesis

6-hydroxymethyl-dihydropterin diphosphate biosynthesis II (archaea)

adenosine 5'-phosphoramidate biosynthesis

archaeosine biosynthesis

callose biosynthesis

candicidin biosynthesis

chlorogenic acid degradation

CMP-legionaminate biosynthesis

cyanide detoxification during fruit ripening

demethylmenaquinol-8 biosynthesis III

diacylglyceryl-N,N,N-trimethylhomoserine biosynthesis

flavonoid biosynthesis (in equisetum)

gallate biosynthesis

laminaribiose biosynthesis

L-rhamnose degradation II

L-rhamnose degradation III

methane oxidation to methanol II

methylaspartate cycle

methylhalide biosynthesis (plants)

nitrate reduction VII (denitrification)

o-diquinones biosynthesis

phytochelatins biosynthesis

S-methyl-5-thiadenosine degradation I

S-methyl-5-thiadenosine degradation II

S-methyl-5-thiadenosine degradation III

S-methyl-5-thio-α-D-ribose 1-phosphate degradation

salidroside biosynthesis

sangivamycin biosynthesis

starch degradation III

starch degradation IV

starch degradation V

sulfoacetaldehyde degradation III

sulfur volatiles biosynthesis

toyocamycin biosynthesis

ubiquinol-8 biosynthesis (prokaryotic)

volatile esters biosynthesis (during fruit ripening)

New Pathways from Plant Metabolic Network (PMN)

carotenoid cleavage dioxygenases

detoxification of reactive carbonyls in chloroplasts

diacylglycerol biosynthesis (PUFA enrichment in oilseed)

fatty acid biosynthesis (plant mitochondria)

phosphatidylcholine acyl editing

pinitol biosynthesis I

pinitol biosynthesis II

poly-hydroxy fatty acids biosynthesis

salicin biosynthesis

salicortin biosynthesis

salicylate glucosides biosynthesis IV

scopoletin biosynthesis

sporopollenin precursor biosynthesis

New Bioenergy-Related Pathways

(1,3)-β-D-xylan degradation

(1,4)-β-D-xylan degradation

cellulose degradation I (cellulolosome)

cellulose degradation II (fungi)

hydrogen production I

hydrogen production II

hydrogen production III

hydrogen production IV

hydrogen production V

hydrogen production VI

hydrogen production VIII

L-arabinan degradation

rhamnogalacturonan type I degradation I (fungi)

rhamnogalacturonan type I degradation II (bacteria)

xyloglucan degradation I (endoglucanase)

xyloglucan degradation II (exoglucanase)

xylose degradation III

New Pathways from HumanCyc

androgen biosynthesis

estrogen biosynthesis

leukotriene biosynthesis

pregnenolone biosynthesis

New Pathways from EcoCyc

curcumin degradation

New Superpathways

superpathway of cellulose and hemicellulose degradation (cellulolosome)

superpathway of hydrogen production

Updated Pathways

DIBOA/DIMBOA biosynthesis

fructan degradation

glutamate degradation II

indole glucosinolate breakdown (insect chewing induced)

methane oxidation to methanol I

pyrimidine ribonucleotides interconversion

suberin biosynthesis

sucrose biosynthesis

trans-lycopene biosynthesis I (bacteria)

trans-lycopene biosynthesis II (plants)

triacylglycerol biosynthesis

Updated Bioenergy-Related Pathways

(1,4)-β-xylan degradation

Updated Superpathways

superpathway of pentose and pentitol degradation  

---

Release Notes for MetaCyc Version 15.0

Released on March 18, 2011

MetaCyc KB Statistics

Pathways	1677
Reactions	9212
Enzymes	7086
Chemical Compounds	9048
Organisms	2099
Citations	27579

New and Updated Pathways

We have added 37_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 17 pathways by adding commentary and updated enzyme and gene information, for a total of 54 new and updated pathways. Of the new pathways, 3 were contributed by PMN (Plant Metabolic Network) curators. We also added 2 new superpathways.

Microbial Metabolism: Under "metabolism of inorganic compounds" we added four new pathways for sulfur metabolism, updated two existing ones, and added a pathway describing iron oxidation by the extreme acidophile Acidithiobacillus ferrooxidans. Under "degradation" we added five pathways for oxalate, the most oxidized two-carbon compound, two pathways for the bacterial degradation of the plant secondary metabolite citronellol and its derivative cis-geranyl-CoA, and pathways describing the fungal degradation of geraniol, nerol, resveratrol, and galactose.In "biosynthesis" we added pathways for mannosylglucosylglycerate and di-myo-inositol phosphate, both compatible solutes common in bacteria adapted to hot environments, and pathways for the antibiotics dehydrophos and jadomycin, which are produced by (different) Streptomyces species. Other new biosynthetic pathways include the biosynthesis of the bacterial signaling compounds quinolone and alkylquinolone (including a superpathway), the bacterial virulence factor pyocyanin, and a fungal pathway for the apocarotenoid neurosporaxanthin. In addition, we added two pathways that together describe the synthesis of queuosine, a modified nucleoside found in certain tRNAs of most organisms, as well as a pathway that describes intron removal (splicing) in archaeal and eukaryotic tRNAs.

Among the updated pathways are a pathway that describes the part of photosynthesis that harvests light energy, the degradation of the aromatic compounds gallate and 4-nitrophenol, and the biosynthesis of the compatible solute glucosylglycerate and the secondary metabolite phenazine-1-carboxylate. We also updated pathways for L-arabinose and xylose degradation in fungi, and L-leucine degradation in bacteria and eukaryotes.

Animal Metabolism: We added a new pathway for the metabolism of thyronamine signaling molecules and updated two pathways for thyroid hormone (thyronine) metabolism in vertebrates, as well as the tRNA splicing pathway mentioned above.

Plant Metabolism: New plant biosynthetic pathways include caffeoylglucarate, an important hydrocinnamic acid found in many plants, the diterpenoid plaunotol used in treating gastric ulcers, the sesquiterpenoid δ-guaiene, which is used medicinally and as incense product, pterostilbene, a close relative of resvertrol that is used in anti-cancer drug research, and tartrate, the principal acid found in wine, contributing important aspects to its taste, mouthfeel and aging potential. Two new plant defense-related pathways were also included, for the breakdown of glucosinolates (1-thio-β-D-glucosides) and the formation of the volatile (C16)-homoterpene (E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene (TMTT)

Among the updated plant pathways were pathways for the biosynthesis of the (C11)-homoterpene (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), and plant sterols, which provide important structural lipids and precursors for plant hormone biosynthesis.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the reactions in MetaCyc with the latest information (as of November 2010) from the Nomenclature Cmmittee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by incorporating the final version of supplement 16 (see http://www.chem.qmul.ac.uk/iubmb/enzyme/supplements/sup2010/). We also updated names and synonyms for enzymes with full EC numbers by incorporating this data from the ExplorEnz database.

List of New and Updated Pathways

New Pathways

2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis

4-hydroxy-2(1H)-quinolone biosynthesis

caffeoylglucarate biosynthesis

cinnamate and 3-hydroxycinnamate degradation to 2-oxopent-4-enoate

cis-genanyl-CoA degradation

citronellol degradation

dehydrophos biosynthesis

di-myo-inositol phosphate biosynthesis

Fe(II) oxidation

galactose degradation IV

geraniol and nerol degradation

glucosylglycerate biosynthesis II

δ-guaiene biosynthesis

jadomycin biosynthesis

mannosylglucosylglycerate biosynthesis I

mannosylglucosylglycerate biosynthesis II

neurosporaxanthin biosynthesis

oxalate biosynthesis

oxalate degradation I

oxalate degradation II

oxalate degradation III

oxalate degradation IV

oxalate degradation V

plaunotol biosynthesis

PreQ₀ biosynthesis

pterostilbene biosynthesis

pyocyanin biosynthesis

queuosine biosynthesis

resveratrol degradation

sulfate reduction III (assimilatory)

sulfur oxidation IV (intracellular sulfur)

thiosulfate oxidation IV (multienzyme complex)

thyronamine and iodothyronamine metabolism

tRNA splicing

New Pathways from Plant Metabolic Network (PMN)

(E,E)-4,8,12-trimethyltrideca-1,3,7,11-tetraene biosynthesis

glucosinolate breakdown (via thiocyanate-forming protein)

tartrate biosynthesis

New Superpathways

superpathway of quinolone and alkylquinolone biosynthesis

superpathway of sulfide oxidation (phototrophic sulfur bacteria)

Updated Pathways

(3E)-4,8-dimethylnona-1,3,7-triene biosynthesis

4-nitrophenol degradation I

gallate degradation I

gallate degradation II

glucosylglycerate biosynthesis I

L-arabinose degradation II

leucine degradation I

phenazine-1-carboxylate biosynthesis

photosynthesis light reactions

plant sterol biosynthesis

sulfate reduction IV (dissimilatory)

thiosulfate oxidation III (multienzyme complex)

thyroid hormone metabolism I (via deiodination)

thyroid hormone metabolism II (via conjugation and/or degradation)

traumatin and (Z)-3-hexen-1-yl acetate biosynthesis

vindoline and vinblastine biosynthesis

xylose degradation II  

---

Release Notes for MetaCyc Version 14.6

Released on December 3, 2010

MetaCyc KB Statistics

Pathways	1642
Reactions	8988
Enzymes	6912
Chemical Compounds	8869
Organisms	2072
Citations	26848

New and Updated Pathways

We have added 55_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 16 pathways by adding commentary and updated enzyme and gene information, for a total of 71 new and updated pathways.  Of the new pathways, 5 were contributed by PMN (Plant Metabolic Network) curators and one was contributed by EcoCyc curators.  We also added 9 new superpathways and updated one existing superpathway.

Microbial Metabolism: During this period we have reorganized and updated the pathways that describe the metabolism of purines, including de novo biosynthesis, salvage, and degradation. Although listed under microbial metabolism, this reorganization of pathways applies to all organisms. We added new pathways that describe the synthesis and degradation of fluorinated organic compounds and several pathways that describe the fermentation of Clostridium acetobutylicum, an important biotechnology organism that can produce acetone, ethanol and butanol under solventogenic conditions, or acetate and 2-butanoate under acidogenic conditions. We added two pathways that describe manganese oxidation, a process that is still not completely understood, but has tremendous influence on the global biogeochemistry of the planet, and particularly the oceans. We added a pathway for degradation of the C2 sulfonate sulfoacetate, as well as several degradation pathways for C3 sulfonates, such as sulfolactate, (R)-cysteate and (S)-2,3-dihydroxypropane-1-sulfonate. We also added novel pathways for salicylate degradation in Streptomyces and yeast.

Also in microbial biosynthesis, we curated a second pathway for the synthesis of coenzyme M as well as new pathways for the biosynthesis of alkanes by cyanobacteria, the exopolysaccharides xanthan and acetan, the potent proteasome inhibitor salinosporamide A, the carotenoid spirilloxanthin and its diketo derivative, CDP-2-glycerol (involved in capsular polysaccharide biosynthesis), rhamnolipids, and the bacterial storage compound polyhydroxydecanoate. In addition, we curated a fungal pathway for the biosynthesis of fusicoccins, which are powerful fungal phytotoxins.

Animal Metabolism: Juvenile hormones regulate several processes in many insect species, including embryonic development, metamorphosis, and reproduction. We have added a pathway that describes the synthesis of the most common such hormone, juvenile hormone III, in the Lepidoptera, and updated an existing pathway with enzymes from the Dictyoptera, Orthoptera and Diptera.

Plant Metabolism: In plant metabolism we added several pathways for the biosynthesis of new secondary metabolites. These include methylketones which are powerful insect repellents produced as plant defense compounds, labdane-type diterpenes which are used as precursor molecules in the perfume industry, C-glycosylflavones, and a pathway for O-methylation of tricetin, a potential nutraceutical. A second pathway for the biosynthesis of ent-kaurene, an important precursor in the biosynthesis of the gibberellin plant hormones, was also added. We also updated pathways for the biosynthesis of oligomeric urushiol and zerumbone.

Three new salicylate glucosides biosynthesis pathways represent ways in which different plant species finely tune the amounts of active salicylate present in their cells. Salicylate is an important plant hormone often associated with the systemic acquired resistance defense response that can also influence other normal developmental processes such as flowering. Finally, we added two new pathways for the biosynthesis of the unusual fatty acids dicranin and sciadonate. Sciadonate is produced primarily by gymnosperms and a few angiosperms, while dicranin is produced in many species of moss. Both of these compounds offer potential pharmaceutical benefits.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the reactions in MetaCyc with the latest information (as of November 2010) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by incorporating the latest version of supplement 16 (see http://www.chem.qmul.ac.uk/iubmb/enzyme/supplements/sup2010/). We also updated names and synonyms for enzymes with full EC numbers by incorporating this data from the ExplorEnz database.

New External Database Links for Compounds and Reactions:

To improve correlation with other databases, we have added the following numbers of new database links from MetaCyc compounds to external databases:  2074 ChEBI compounds, 629 PubChem compounds and 93 KEGG compounds.  We also updated 491 database links to ChEBI, 366 to PubChem and 15 to KEGG.  A total of 4376 MetaCyc compounds are now linked to KEGG, 3212 to ChEBI and 8166 to PubChem.  We have also curated 545 new database links from MetaCyc reactions to KEGG reactions.  A total of 3755 MetaCyc reactions are now linked to KEGG.

List of New and Updated Pathways

New Pathways

2,3-dihydroxypropane-1-sulfonate degradation

acetan biosynthesis

adenine and adenosine salvage II

adenine and adenosine salvage III

adenine and adenosine salvage IV

adenine and adenosine salvage V

adenine and adenosine salvage VI

adenosine nucleotides degradation I

adenosine nucleotides degradation III

CDP-2-glycerol biosynthesis

C-glycosylflavone biosynthesis

coenzyme M biosynthesis II

ent -kaurene biosynthesis II

fluoroacetate and fluorothreonine biosynthesis

fluoroacetate degradation

fusicoccins biosynthesis

glycolate and glyoxylate degradation III

guanine and guanosine salvage I

guanine and guanosine salvage II

guanine and guanosine salvage III

guanosine nucleotides degradation I

guanosine nucleotides degradation II

guanosine nucleotides degradation III

heptadecane biosynthesis

juvenile hormone III biosynthesis II

L-1-phosphatidyl-inositol biosynthesis (Mycobacteria)

labdane-type diterpenes biosynthesis

manganese oxidation I

manganese oxidation II

methylketone biosynthesis

O -methylation of tricetin

phosphopantothenate biosynthesis III

polyhydroxydecanoate biosynthesis

pyruvate fermentation to acetone

pyruvate fermentation to butanol

pyruvate fermentation to ethanol III

(R)-cysteate degradation

rhamnolipid biosynthesis

salicylate degradation III

salicylate degradation IV

salinosporamide A biosynthesis

spirilloxanthin and 2,2'-diketo-spirilloxanthin biosynthesis

sulfoacetate degradation

sulfolactate degradation I

sulfolactate degradation II

sulfolactate degradation III

tetrahydrofolate biosynthesis

tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate

xanthan biosynthesis

New Pathways from Plant Metabolic Network (PMN)

dicranin biosynthesis

salicylate glucosides biosynthesis I

salicylate glucosides biosynthesis II

salicylate glucosides biosynthesis III

sciadonic acid biosynthesis

New Pathways from EcoCyc

sedoheptulose bisphosphate bypass

New Superpathways

superpathway of Clostridium acetobutylicum acidogenic and solventogenic fermentation

superpathway of Clostridium acetobutylicum acidogenic fermentation

superpathway of Clostridium acetobutylicum solventogenic fermentation

superpathway of guanosine nucleotides degradation (plants)

superpathway of phenylalanine biosynthesis

superpathway of sulfolactate degradation

superpathway of tetrahydrofolate biosynthesis

superpathway of tryptophan biosynthesis

superpathway of tyrosine biosynthesis

Updated Pathways

2-aminoethylphosphonate degradation

adenine and adenosine salvage I

caffeine degradation III (bacteria, via demethylation)

caffeine degradation IV (bacteria, via demethylation and oxidation)

caffeine degradation V (bacteria, to trimethylurate)

camalexin biosynthesis

coumestrol biosynthesis

glutamate removal from folates

juvenile hormone III biosynthesis I

oligomeric urushiol biosynthesis

phenylacetate degradation I (aerobic)

polyhydroxybutyrate biosynthesis

vernolic acid biosynthesis

very long chain fatty acid biosynthesis

xanthine and xanthosine salvage

zerumbone biosynthesis

Updated Superpathways

superpathway of tetrahydrofolate biosynthesis and salvage

---

Release Notes for MetaCyc Version 14.5

Released on October 1, 2010

MetaCyc KB Statistics

Pathways	1583
Reactions	8837
Enzymes	6758
Chemical Compounds	8763
Organisms	2007
Citations	26009

New and Updated Pathways

We have added 56_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 8 pathways by adding commentary and updated enzyme and gene information, for a total of 64 new and updated pathways.  Of the new pathways, 7 were contributed by PMN (Plant Metabolic Network) curators.  We also added 4 new superpathways and updated 1 superpathway.

Microbial Metabolism: Apart from oxygenic photosynthesis, very few metabolic reactions are known to produce molecular oxygen. Among the pathways included in this release are three examples of these unusual reactions, including chlorate and perchlorate reduction and "intra-aerobic nitrite reduction" - an intriguing pathway despite the fact that the enzymes have not been identified yet. Another interesting pathway is the first full description of biotin biosynthesis (see biotin biosynthesis I).  We also added a frequent variant of pyrimidine deoxyribonucleotides de novo biosynthesis, another siderophore biosynthesis pathway for achromobactin, as well as the aspartate-semialdehyde derived pathways for spermidine and norspermidine biosynthesis and a corresponding superpathway.  Among other additions are degradation pathways for the aromatic pollutants diphenylamine, aniline, phenylethylamine and carbazole, the degradation of caffeine by soil bacteria, the metabolism of mammalian bile salts by gut bacteria, and a pathway describing the mannitol cycle in a protozoan parasite

Animal Metabolism: In animal metabolism we added several pathways that describe the biosynthesis and degradation of the important glycosaminoglycans dermatan sulfate, chondroitin sulfate, and heparan sulfate. These polymeric compounds, which are composed of repeating disacchride units of variable composition and sulfation patterns, are prevalent in connective tissues, but also play important roles in regulation and have been implicated in cardiovascular disease, tumorigenesis, infection, wound repair, and fibrosis.  Defects in enzymes involved in the degradation of these compounds are also involved in several neurodegenerative diseases, including Tay-Sachs.

Plant Metabolism: We curated new pathways for stellariose and lychnose oligosaccharide biosynthesis, along with a lychnose degradation pathway.  We also added the intracellularly segregated plastidial biosynthesis of p-aminobenzoate (PABA).  Two new secondary metabolic pathways were curated for the biosynthesis of the cysteinesulfoxide petivericin, and the flavonoid phloridzin which is a potential drug for the control of blood sugar.  We also added a superpathway that describes the biosynthesis of 1D-myo-inositol hexakisphosphate (phytate), an important storage form of myo-inositol, phosphate and mineral nutrients for utilization during seed germination and seedling growth.

Additions made by the PMN curators include a pathway for the biosynthesis of juvenile hormone III, a compound that normally acts as a developmental regulator in insects but that may be used by plants to affect insect growth or to deter the growth of nearby plants; a pathway for converting the bioactive plant hormones brassinosteroids to their 26-hydroxylated inactive forms; a pathway for the degradation of caffeine, which helps to explain a strategy plants use to balance and control the content of caffeine that accumulates in different cultivars, tissues and at different developmental stages; a pathway that provides an alternative route for glutamine biosynthesis that helps plants to salvage nitrogen from the proteins in senescing leaves for remobilization and transport into developing seeds; a plant variant of a pathway for pyrimidine ribonucleosides degradation; and a salvage pathway for recycling the prenyl tag from farnesylated proteins to prevent the build-up of deleterious compounds and to provide  building blocks for isoprenoid biosynthesis as well as regulatory protein prenylation.

Other Improvements

Update of EC Reactions:

During this quarter we have updated the reactions in MetaCyc with the latest information (as of April 2010) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by incorporating the latest version of supplement 16 (see http://www.chem.qmul.ac.uk/iubmb/enzyme/supplements/sup2010/).

Update of NCBI Taxonomy:

We have updated the organism taxonomy component of MetaCyc to match the NCBI Taxonomy Database as of 07/07/2010.

New addition of monoisotopic mass to compounds:

To facilitate analysis of metabolomics data in BioCyc, we augmented the compound search form on our Web site to allow searching for a list of monoisotopic molecular weight values, of the type produced by high-resolution mass spectrometry.  It can be accessed from the menu item Search->Compounds.  Our initial implementation of mass-spec support is rather basic, although it allows changing the tolerance in ppm increments.  It assumes the user will preprocess the data values to add or subtract constant groups such as protons.  The search results are presented in a table that allows easy linking to compound pages, to simplify the identification of plausible candidates for each weight value.  We would appreciate feedback regarding desired additional features for future improvements.

List of New and Updated Pathways

New Pathways

1D-myo-inositol hexakisphosphate biosynthesis V (from Ins(1,3,4)P3)

4-aminobutyrate degradation I

4-aminobutyrate degradation III

7-keto-8-aminopelargonate biosynthesis I

7-keto-8-aminopelargonate biosynthesis II

achromobactin biosynthesis

aniline degradation

biotin biosynthesis I

caffeine degradation (bacteria)

carbazole degradation

chlorate reduction

chondroitin and dermatan biosynthesis

chondroitin sulfate and dermatan sulfate degradation I (bacterial)

chondroitin sulfate biosynthesis

chondroitin sulfate biosynthesis (late stages)

chondroitin sulfate degradation (metazoa)

costunolide biosynthesis II

dermatan sulfate biosynthesis

dermatan sulfate biosynthesis (late stages)

dermatan sulfate degradation (metazoa)

diphenylamine degradation

glycoaminoglycan-protein linkage region biosynthesis

glycocholate metabolism (bacteria)

guanine and guanosine salvage

heparan sulfate biosynthesis

heparan sulfate biosynthesis (late stages)

intra-aerobic nitrite reduction

limonene degradation III (to perillate)

lychnose biosynthesis

mannitol cycle

tetrahydrofolate-L-glutamate biosynthesis (plants)

N-acetylglucosamine degradation II

nonaprenyl diphosphate biosynthesis II

norspermidine biosynthesis

perchlorate reduction

petivericin biosynthesis

phenylethylamine degradation II

phloridzin biosynthesis

plastidial PABA biosynthesis in plants

pyrimidine deoxyribonucleotides de novo biosynthesis II

spermidine biosynthesis II

stachyose degradation

stellariose and mediose biosynthesis

New Pathways from Plant Metabolic Network (PMN)

brassinosteroids inactivation

caffeine degradation I (main, plants)

caffeine degradation II

farnesylcysteine salvage pathway

glutamine biosynthesis III

juvenile hormone III biosynthesis

pyrimidine ribonucleosides degradation II

New Pathways from BsubCyc

bacillithiol biosynthesis

New Pathways from EcoCyc

ethanolamine utilization

tRNA processing pathway

New Pathways from HumanCyc

flavin biosynthesis IV (mammalian)

ketogenesis

sucrose degradation V (mammalian)

New Superpathways

superpathway of 1D-myo-inositol hexakisphosphate biosynthesis (plants)

superpathway of C28 brassinosteroid biosynthesis

superpathway of microbial D-galacturonate and D-glucuronate degradation

superpathway of polyamine biosynthesis III

Updated Pathways

(1'S,5'S)-averufin biosynthesis

4-aminobutyrate degradation IV

brassinosteroid biosynthesis I

brassinosteroid biosynthesis II

cholate degradation (bacteria, anaerobic)

lactose degradation II

trans-lycopene biosynthesis II (plants)

Updated Superpathways

superpathway of 4-aminobutyrate degradation

Pathways that were newly updated in EcoCyc

phenylacetate degradation I (aerobic)

---

Release Notes for MetaCyc Version 14.1

Released on June 16, 2010

MetaCyc KB Statistics

Pathways	1531
Reactions	8676
Enzymes	6524
Chemical Compounds	8732
Organisms	1914
Citations	24423

 

New and Updated Pathways

We have added 67_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 37 pathways by adding commentary and updated enzyme and gene information, for a total of 104 new and updated pathways.  Of the new pathways, 16 were contributed by PMN (Plant Metabolic Network) curators.

Microbial Metabolism: One of the main topics in our curation of microbial metabolism during this release was peptidoglycan biosynthesis. We revised our current pathways and added new ones to cover more details of this important process, such as amidation of L-glutamate residues in the pentapeptide component, formation of cross-bridges, and trans-peptidation. We added new variants that describe peptidoglycan biosynthesis in important pathogens among the staphylococci, mycobacteria and enterococci, as well as new pathways that explain the nature of resistance to antibiotics that interfere with peptidoglycan synthesis, such as β-lactams, vancomycin and teicoplanin.

Other additions include pathways for the biosynthesis of vitamin B₆ (pyridoxal 5'-phosphate), the cofactor molybdopterin cytosine dinucleotide, the cell surface lipopolysaccharide component GDP-D-glycero-α-D-manno-heptose, and the rare amino acid 3-methylarginine, which is used as an antibiotic by the epiphyte Pseudomonas syringae.  Other new pathways described the degradation of uracil, thymine, polyvinyl alcohol, anthranilate, tryptophan, methanol, D-galacturonate, D-glucuronate, and the pectin metabolite 5-dehydro-4-deoxy-D-glucuronate.  We also curated four fungal alkaloid pathways involved in the biosynthesis of ergot and its derivatives.

Animal Metabolism: In animal metabolism we added a pathway for the degradation of hemoglobin that is found in species of the malaria parasite Plasmodium, and a pathway for the biosynthesis of diphthamide, a unique posttranslationally modified histidine residue found only in translation elongation factor 2.  We also curated pathways for the biosynthesis of the common pigment eumelanin and the biosynthesis of L-dopachrome, an important intermediate in the synthesis of most types of melanins.

Plant Metabolism:  We curated six new monoterpene biosynthesis pathways whose products are used in cosmetic fragrances and as food additives. We also added two new ω-hydroxylated fatty acid biosynthesis pathways and three new fatty acid biosynthesis pathways including ricinoleate and stigma estolide biosynthesis.  Stigma estolide is a naturally occurring lipid-based polyester.  One new GABA shunt pathway was added in plant primary metabolism, along with a sitosterol biosynthetic pathway involved in plant defense.

PMN curators have focused their attention on expanding and improving the coverage of pathways related to plant defense compounds, signaling compounds, polyamines, and sphingolipids. In the area of plant defense, several new pathways have been added for compounds that are important in combating biotic threats, such as hordatine, an antifungal compound that is abundant in young barley seeds. In addition, substantial revisions have been made to a large number of pathways describing the biosynthesis of glucosinolates. These compounds, produced by broccoli, mustard, and other related plants, contribute to plant defense, but, also influence the aroma, flavor, and nutritional benefits of these foods for humans.

New pathways related to the inactivation of gibberellins, a major class of plant hormones that stimulate growth, have also been added, as well as pathways related to the production of volatile benzoates that can contribute to floral aromas. Three pathways related to polyamines, important nitrogen-rich compounds, have been added, and the plant variant of the pathway describing the production of sphingolipids, which serve as important cell membrane components, has been substantially revised.

List of New and Updated Pathways

New Pathways

3-carene biosynthesis

3-methylarginine biosynthesis

4-aminobutyrate degradation IV (plants)

5-dehydro-4-deoxy-D-glucuronate degradation

agroclavine biosynthesis

anthranilate degradation IV (aerobic)

D-galactarate degradation II

D-galacturonate degradation II

D-galacturonate degradation III

D-glucarate degradation II

D-glucuronate degradation II

diphthamide biosynthesis

ergot alkaloid biosynthesis

ergotamine biosynthesis

eumelanin biosynthesis

fenchol biosynthesis I

fenchol biosynthesis II

fenchone biosynthesis

fumigaclavine C biosynthesis

GDP-D-glycero-α-D-manno-heptose biosynthesis

hemoglobin degradation

hydrogen oxidation III (anaerobic, NADP)

hydroxylated fatty acid biosynthesis (plants)

KDO transfer to lipid IV_A II (Chlamydia)

L-dopachrome biosynthesis

methanol oxidation to formaldehyde II

methanol oxidation to formaldehyde III

molybdopterin cytosine dinucleotide biosynthesis

ω- hydroxylation of laurate

ω-hydroxylation of caprate and laurate

peptidoglycan biosynthesis IV (Enterococcus faecium)

peptidoglycan biosynthesis V (β-lactam resistant)

peptidoglycan cross-bridge biosynthesis I (S. aureus)

peptidoglycan cross-bridge biosynthesis II (E. faecium)

peptidoglycan cross-bridge biosynthesis III (Enterococcus faecalis)

peptidoglycan cross-bridge biosynthesis IV (Weissella viridescens)

perillyl alcohol biosynthesis

polyvinyl alcohol degradation

pyridoxal 5'-phosphate biosynthesis II

ricinoleate biosynthesis

sitosterol biosynthesis

stigma estolide biosynthesis

thymine degradation

trichome monoterpenes biosynthesis

tryptophan degradation XII (Geobacillus)

uracil degradation (oxidative)

vancomycin resistance I

vancomycin resistance II

New Pathways from Plant Metabolic Network (PMN)

4-hydroxybenzoate biosynthesis IV

4-hydroxybenzoate biosynthesis V

benzoate biosynthesis II (CoA-independent, non-β-oxidative)

benzoate biosynthesis III (CoA-dependent, non-β-oxidative)

ceramide degradation

curcuminoid biosynthesis

gibberellin inactivation II (methylation)

gibberellin inactivation III (epoxidation)

hordatine biosynthesis

oxidized GTP and dGTP detoxification

phenylphenalenone biosynthesis

rotenoid biosynthesis II

serinol biosynthesis

spermidine hydroxycinnamic acid conjugates biosynthesis

spermine and spermidine degradation II

spermine and spermidine degradation III

New Pathways from EcoCyc

D-malate degradation

trehalose degradation VI (periplasmic)

uracil degradation III

Updated Pathways

aldoxime degradation

aliphatic glucosinolate biosynthesis, side chain elongation cycle

benzoyl-CoA degradation I (aerobic)

glucosinolate biosynthesis from dihomomethionine

glucosinolate biosynthesis from hexahomomethionine

glucosinolate biosynthesis from homomethionine

glucosinolate biosynthesis from pentahomomethionine

glucosinolate biosynthesis from phenylalanine

glucosinolate biosynthesis from tetrahomomethionine

glucosinolate biosynthesis from trihomomethionine

glucosinolate biosynthesis from tryptophan

homomethionine biosynthesis

morphine biosynthesis

nicotinate degradation I

nitrogen fixation

peptidoglycan biosynthesis I (meso-diaminopimelate containing)

peptidoglycan biosynthesis II (staphylococci)

peptidoglycan biosynthesis III (mycobacteria)

phosphate acquisition

rhizobactin 1021 biosynthesis

sorgoleone biosynthesis

sphingolipid biosynthesis (plants)

trans-cinnamoyl-CoA biosynthesis

trans-zeatin biosynthesis

UDP-D-glucuronate biosynthesis (from myo-inositol)

uracil degradation (reductive)

Pathways that were newly updated in EcoCyc

formylTHF biosynthesis I

glucose and glucose-1-phosphate degradation

L-cysteine degradation

lipid A-core biosynthesis

NAD phosphorylation and dephosphorylation

ppGpp biosynthesis

pyridoxal 5ﾂ’-phosphate biosynthesis

Salvage pathways of guanine, xanthine, and their nucleosides

superpathway of lipopolysaccharide biosynthesis

thioredoxin pathway

tryptophan biosynthesis

---

Release Notes for MetaCyc Version 14.0

Released on March 18, 2010

MetaCyc KB Statistics

Pathways	1471
Reactions	8409
Enzymes	6198
Chemical Compounds	8572
Organisms	1861
Citations	22459

 

New and Updated Pathways

We have added 41_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 12 pathways by adding commentary and updated enzyme and gene information, for a total of 53 new and updated pathways.  We also added 3 new superpathways.

Microbial Metabolism:  We added several pathways for the biosynthesis of siderophores - the small, high-affinity iron chelating compounds secreted by microorganisms for scavenging iron.  New pathways describe the biosynthesis of alcaligin, bisucaberin, desferrioxamine B, desferrioxamine E, putrebactin,  pyochelin, pyoverdine I, vibriobactin and yersiniabactin.  We significantly expanded our coverage of acetoin and butanediol metabolism, and added pathways for the biosynthesis of the mycolyl-arabinogalactan-peptidoglycan complex, an important component of the mycobacterial cell wall.  We also added new pathways for the biosynthesis of salicylate and of the enzyme cofactor pyrroloquinoline quinone, and for the degradation of L-quinate, D-arginine, shikimate and arsenate.

Animal Metabolism:  We extended our coverage of antioxidants with another pathway for ascorbate biosynthesis, an ascorbate recycling pathway found in the cytosol and a pathway for α-tocopherol degradation.  We also added three pathways for enzymatic degradation of the hormone melatonin.

Plant Metabolism:  We continued our coverage of plant secondary metabolism with the addition of pathways for the biosynthesis of 4-hydroxycoumarin, a plant polyketide that is released only by the action of fungi on plant material, and hispidol, a compound involved in plant defense. We also added three pathways for the degradation of ginsenosides, two of which occur in fungi and one in the ginseng plant itself.  In primary metabolism we added a novel shunt pathway for accumulation of the micronutrient selenium in plants and a phosphate utilization pathway implicated in plant cell wall regeneration.

Other Improvements

Update of EC Reactions

During this quarter we have updated the reactions in MetaCyc with the latest information (as of November 2009) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by incorporating the final version of supplement 15 (see Enzyme Nomenclature Supplement 15)

Update of NCBI Taxonomy

We have updated the organism taxonomy component of MetaCyc to match the NCBI Taxonomy Database as of 01/11/2010.

List of New and Updated Pathways

New Pathways

4-hydroxycoumarin biosynthesis

α-tocopherol degradation

alcaligin biosynthesis

arsenate detoxification III (mycothiol)

ascorbate biosynthesis VII

ascorbate recycling (cytosolic)

bisucaberin biosynthesis

carrageenan biosynthesis

D-arginine degradation

desferrioxamine B biosynthesis

desferrioxamine E biosynthesis

ginsenoside degradation I

ginsenoside degradation II

ginsenoside degradation III

hispidol biosynthesis

melatonin degradation I

melatonin degradation II

melatonin degradation III

meso-butanediol biosynthesis I

meso-butanediol biosynthesis II

mono-trans, poly-cis decaprenyl phosphate biosynthesis

mycolyl-arabinogalactan-peptidoglycan complex biosynthesis

peptidoglycan biosynthesis IV (mycobacteria)

phosphate utilization in cell wall regeneration

putrebactin biosynthesis

pyochelin biosynthesis

pyoverdine I biosynthesis

pyrroloquinoline quinone biosynthesis

quinate degradation II

Rapoport-Luebering glycolytic shunt

salicylate biosynthesis I

Se volatilization (in Se accumulator plants)

shikimate degradation II

(S)-acetoin biosynthesis

(S,S)-butanediol biosynthesis

(S,S)-butanediol degradation

UDP-N-acetylmuramoyl-pentapeptide biosynthesis I (generic)

UDP-N-acetylmuramoyl-pentapeptide biosynthesis II (lysine-containing)

UDP-N-acetylmuramoyl-pentapeptide biosynthesis III (meso-DAP)

vibriobactin biosynthesis

yersiniabactin biosynthesis

New Superpathways

superpathway of 2,3-butanediol biosynthesis

superpathway of mycolyl-arabinogalactan-peptidoglycan complex biosynthesis

superpathway of melatonin degradation

Updated Pathways

alkylnitronates degradation

ammonia oxidation II (anaerobic)

glucosinolate breakdown

mycothiol biosynthesis

nitroethane degradation

phenylalanine biosynthesis I

quinate degradation I

(R,R)-butanediol degradation

rubber biosynthesis

shikimate degradation I

streptomycin biosynthesis

tyrosine biosynthesis I

---

Release Notes for MetaCyc Version 13.6

Released on November 21, 2009

MetaCyc KB Statistics

Pathways	1436
Reactions	8248
Enzymes	6056
Chemical Compounds	8363
Organisms	1834
Citations	21713

 

New and Updated Pathways

We have added 43_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 8 pathways by adding commentary and updated enzyme and gene information, for a total of 51 new and updated pathways.  Of the new pathways, 2 were contributed by PMN (Plant Metabolic Network) curators.  We also added 2 new superpathways.

Microbial Metabolism:  Among the additions to microbial metabolism are pathways for the biosynthesis of the indolocarbazole alkaloids rebeccamycin, K-252 and staurosporine. These actinobacterial secondary metabolites, along with related and derived compounds, are known to act as potent inhibitors of DNA topoisomerases and protein kinases. We also added several pathways for the degradation of lignin-derived compounds, including syringate, ferulate, vanillin, vanillate, 5,5'-dehydrodivanillate and guaiacylglycerol-β-guaiacyl ether. We completed our coverage of protocatechuate degradation by adding a third pathway that describes para-cleavage of this important intermediate of aromatic compounds degradation. In sulfur metabolism we added pathways for homotaurine degradation and tetrathionate oxidation. Other additions include a pathway used by marine bacteria that degrade acrylate, and yet another pathway for degradation of L-lysine.

In archaeal metabolism we added pathways for the biosynthesis of CDP-archaeol, the precursor of all archaeal phospholipids, and of the phospholipid archaetidylinositol.

Animal Metabolism:  We added several pathways that cover the metabolism of inositol phosphates, a group of compounds that includes several important secondary messengers and other compounds that play key roles in signal transduction. Several pathways describe the metabolism of 3-phosphoinositides, D-myo-inositol (1,4,5)-trisphosphate, D-myo-inositol (1,4,5,6)-tetrakisphosphate and D-myo-inositol (3,4,5,6)-tetrakisphosphate. Additional pathways describe several routes for the biosynthesis of D-myo-inositol hexakisphosphate (phytate) and of inositol pyrophosphate compounds.  We also included pathways for the degradation of L-dopa, noradrenaline and adrenaline, purines, and phenylalanine via decarboxylation or transamination of its side chain.

Plant Metabolism:  We continued to expand our coverage of plant secondary metabolites.  We added a pathway for the biosynthesis of echinatin, a retrochalcone that is one of several secondary metabolites present in licorice, a substance derived from the root and rhizome of the genus Glycyrrhiza. We also added a pathway for the biosynthesis of coumestrol, a coumestan isoflavone found in many leguminous plants, many of which act as phytoestrogens in mammals.  Other new pathways include the biosynthesis of flavonol glucosides, the protoberberine alkaloid dehydroscoulerine, the cytotoxic alkaloid camptothecin, phaselic acid, and benzoylanthranilate, the precursor of dianthranmides.  We also added a pathway for phosphate acquisition and updated a previously curated pathway for ethylene biosynthesis from methionine.

Other Improvements

New External Database Links for Compounds:  

To improve correlation with other databases, we have added the following numbers of new database links from MetaCyc compounds to external databases: 105 ChEBI compounds, 503 PubChem compounds and 504 KEGG compounds.  A total of 4311 MetaCyc compounds are now linked to KEGG.

List of New and Updated Pathways

New Pathways

3-phosphoinositide biosynthesis

3-phosphoinositide degradation

5,5'-dehydrodivanillate degradation

acetaldehyde biosynthesis I

acetaldehyde biosynthesis II

acrylate degradation

archaetidylinositol biosynthesis

benzoylanthranilate biosynthesis

camptothecin biosynthesis

CDP-archaeol biosynthesis

D-myo-inositol (1,3,4)-trisphosphate biosynthesis

D-myo-inositol (1,4,5)-trisphosphate biosynthesis

D-myo-inositol (1,4,5)-trisphosphate degradation

D-myo-inositol (1,4,5,6)-tetrakisphosphate biosynthesis

D-myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis

D-myo-inositol-5-phosphate metabolism

D-myo-inositol hexakisphosphate biosynthesis I

D-myo-inositol hexakisphosphate biosynthesis II (mammalian)

D-myo-inositol hexakisphosphate biosynthesis IV (Dictyostelium)

dehydroscoulerine biosynthesis

ferulate degradation

flavonol glucosylation I

guaiacylglycerol-β-guaiacyl ether degradation

homotaurine degradation

inositol pyrophosphates biosynthesis

K-252 biosynthesis

L-dopa degradation

lysine degradation X

noradrenaline and adrenaline degradation

ornithine degradation II (Stickland reaction)

phaselic acid biosynthesis

phenylalanine degradation IV (mammalian, via side chain)

phosphate acquisition

phosphinothricin tripeptide biosynthesis

protocatechuate degradation III (para-cleavage pathway)

purine degradation IV (aerobic)

rebeccamycin biosynthesis

staurosporine biosynthesis

syringate degradation

tetrathionate oxidation

vanillin and vanillate degradation

New Pathways from Plant Metabolic Network (PMN)

coumestrol biosynthesis

echinatin biosynthesis

New Superpathways

superpathway of D-myo-inositol (1,4,5)-trisphosphate metabolism

superpathway of inositol phosphate compounds

Updated Pathways

arginine, ornithine and proline interconversion

ethylene biosynthesis from methionine

gallate degradation II

lysine degradation VI

methylgallate degradation

protocatechuate degradation I (meta-cleavage pathway)

superpathway of sulfide oxidation (Acidithiobacillus ferrooxidans)

xylogalacturonan biosynthesis

 

---

Release Notes for MetaCyc Version 13.5

Released on Oct 7th, 2009

MetaCyc KB Statistics

Pathways	1399
Reactions	8094
Enzymes	5857
Chemical Compounds	8221
Organisms	1795
Citations	20860

 

New and Updated Pathways

We have added 46_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 13 pathways by adding commentary and updated enzyme and gene information, for a total of 64 new and updated pathways.  Of the new pathways, 2 were contributed by PMN (Plant Metabolic Network) curators (www.plantcyc.org).  We also added 8 new superpathways.

Microbial Metabolism:  We added an RNA-dependent cysteine biosynthesis pathway found in the Euryarchaeota, two pathways for the salvage of adenosylcobalamin, several pathways describing biosynthesis of carotenoid compounds in bacteria, including neurosporin, zeaxanthin-β-D-diglucoside, synechoxanthin, myxol-2' fucoside and spheroidene, a pathway for the biosynthesis of the siderophore petrobactin, a novel pathway for the biosynthesis of the common electron carrier menaquinone, and a pathway for the biosynthesis of the fatty acid palmitoleate. We also created a superpathway describing the complete biosynthesis of fatty acids in E. coli and imported a pathway for methylthioadenosine degradation from EcoCyc.

Animal Metabolism:  We added a pathway for the biosynthesis of selenocysteine that is found in both eukaryotes and archaea.  We also covered thyroid hormone biosynthesis and metabolism, pathways for the degradation of tryptophan and serotonin, and pathways for the biosynthesis of phosphatidylethanolamine and cysteine.

Plant Metabolism:  We enhanced our coverage of glucosinolates, a class of nitrogen and sulfur containing secondary metabolites involved in plant pathogen defense.  New pathways included glucosinolate biosynthesis from di-, tri-, tetra-, penta- and hexahomomethionine, as well as two breakdown (activation) pathways of indole glucosinolates.  We also added a plant pathway for isoprene biosynthesis.  Isoprene emissions from trees and other plants have a major effect on atmospheric chemistry.  In addition, we curated a pathway for methyl indole-3-acetate interconversion showing one of several ways that plants can modulate the biological activity of this hormone.

Also in plant metabolism we covered the biosynthesis of 12 new plant sesquiterpenoids including the phytotoxin botrydial, plant defense compounds curcumene and bergamotene,  and compounds used in the flavor, fragrance and drug industries.  We also curated four new polyketide biosynthetic pathways and pathways for biosynthesis of the diterpenoid  phytoalexin casbene, the polyamine putrescine, the terpenophenolic compound olivetol involved in plant defense, and the hormone tuberonate glucoside.  In addition, we added an aldehyde oxidation pathway, a pathway for dihydroconiferyl aldehyde biosynthesis and we reviewed an existing homogalacturonan degradation pathway.

Other Improvements

New External Database Links for Compounds and Reactions:

To improve correlation with other databases, we have added the following numbers of new database links from MetaCyc compounds and reactions to external databases: 922 KEGG compounds, 304 ChEBI compounds, 900 PubChem compounds, and 3269 KEGG reactions.

We thank Dr. Daniel Kliebenstein of the University of California Davis for providing valuable feedback on glucosinolate pathway curation.

List of New and Updated Pathways

New Pathways

β-caryophyllene biosynthesis

β-cubebene biosynthesis

adenosylcobalamin salvage from cobalamin

adenosylcobalamin salvage from cobinamide II

aldehyde oxidation I

aloesone biosynthesis II

aromatic polyketides biosynthesis

barbaloin biosynthesis

bergamotene biosynthesis I

bergamotene biosynthesis II

botrydial biosynthesis

casbene biosynthesis

curcumene biosynthesis

cysteine biosynthesis II (RNA-dependent)

demethylmenaquinone-8 biosynthesis II

eudesmol biosynthesis

myxol-2' fucoside biosynthesis

neurosporene biosynthesis

olivetol biosynthesis

palmitoleate biosynthesis I

patchoulol biosynthesis

petrobactin biosynthesis

phosphatidylethanolamine biosynthesis III

plumbagin biosynthesis

putrescine biosynthesis IV

santalene biosynthesis

selenocysteine biosynthesis II (archaea and eukaryotes)

selinene biosynthesis

serotonin degradation

spheroidene and spharoidenone biosynthesis

synechoxanthin biosynthesis

thyroid hormone biosynthesis

thyroid hormone metabolism I (via deiodination)

thyroid hormone metabolism II (via conjugation and/or degradation)

tryptophan degradation X (mammalian, via tryptamine)

tuberonate glucoside biosynthesis

valencene and 7-epi-α-selinene biosynthesis

zeaxanthin-β-D-diglucoside biosynthesis

zerumbone biosynthesis

New Pathways from Plant Metabolic Network (PMN)

aliphatic glucosinolate biosynthesis, side chain elongation cycle

dihydroconiferyl aldehyde biosynthesis

glucosinolate biosynthesis from dihomomethionine

glucosinolate biosynthesis from hexahomomethionine

glucosinolate biosynthesis from pentahomomethionine

glucosinolate biosynthesis from tetrahomomethionine

glucosinolate biosynthesis from trihomomethionine

indole glucosinolate breakdown (active in intact plant cell)

indole glucosinolate breakdown (insect chewing induced)

isoprene biosynthesis

methyl indole-3-acetate interconversion

New Pathways from EcoCyc

methylthioadenosine degradation

New Superpathways

cysteine biosynthesis III (mammalia)

cysteine biosynthesis IV (fungi)

superpathway of flavones and derivatives biosynthesis

superpathway of menaquinone-8 biosynthesis II

superpathway of 5-aminoimidazole ribonucleotide biosynthesis

superpathway of unsaturated fatty acids biosynthesis (E. coli)

superpathway of fatty acids biosynthesis (E. coli)

tryptophan degradation XI (mammalian, via kynurenine)

Updated Pathways

(S)-reticuline biosynthesis I

abietic acid biosynthesis

astaxanthin iosynthesis

chorismate biosynthesis I

cysteine biosynthesis I

fluorene degradation I

galactose degradation I (Leloir pathway)

homogalacturonan degradation

jasmonic acid biosynthesis

phytyl diphosphate biosynthesis

proanthocyanidin biosynthesis from flavanols

superpathway of heme biosynthesis from uroporphyrinogen-III

ternatin C5 biosynthesis

---

Release Notes for MetaCyc Version 13.1

Released on June 19, 2009

MetaCyc KB Statistics

Pathways	1355
Reactions	7837
Enzymes	5792
Chemical Compounds	7979
Organisms	1735
Citations	19994

 

New and Updated Pathways

We have added 56_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 10 pathways by adding commentary and updated enzyme and gene information, for a total of 66 new and updated pathways.  Of the new pathways, eight were contributed by PMN (Plant Metabolic Network) curators (www.plantcyc.org).  We also added six new superpathways, one of which was contributed by PMN.

During this release we have expanded our coverage of microbial pathways for the degradation of aromatic compounds, with an emphasis on chloro-substitution.  Other fields that received special attention were archaeal metabolic pathways and the biosynthesis of bacterial auto-inducer compounds.

In animal metabolism, we added pathways for the biosynthesis of dolichol and dolichyl-phosphate, creatine-phosphate, histamine and four pathways for the biosynthesis of CMP-sialic acid derivatives.  We also added a histamine degradation pathway.

In plant metabolism we curated pathways for biosynthesis of the plant hormones indole-3-acetyl amino acids, jasmonyl amino acids and hydroxyjasmonate sulfate, as well as the flavonoids quercetinsulphates, chrysoeriol and luteolin glycosides.  In addition, we added pathways for thiamine (vitamin B1) biosynthesis, serine racemization and calamenene terpenoid biosynthesis.

Other Improvements

During this release period all MetaCyc compounds have been indexed in the NCBI PubChem database and 6,774 corresponding links from MetaCyc to PubChem have been either updated or added.

We thank Dr. Kuni Takayama from the William S. Middleton Memorial Veterans Hospital, Madison, WI for his useful advice concerning the Mycobacterium tuberculosis mycolate biosynthesis pathway.

List of New and Updated Pathways

New Pathways

2,4,5-trichlorophenoxyacetate degradation

2,4,6-trichlorophenol degradation

2,4-dichlorotoluene degradation

2,5-dichlorotoluene degradation

2-aminophenol degradation

2-chlorobenzoate degradation

3,4-dichlorobenzoate degradation

3,4-dichlorotoluene degradation

3-chlorobenzoate degradation II (via protocatechuate)

3-chlorobenzoate degradation III (via gentisate)

3-chlorocatechol degradation II (ortho)

3-chlossrocatechol degradation III (meta pashsway)

3-dehydroquinate biosynthesis I

3-dehydroquinate biosynthesis II (archaea)

4-chlorobenzoate degradation

4-methylcatechol degradation (ortho cleavage)

6-hydroxymethyl-dihydropterin diphosphate biosynthesis

archaetidylserine biosynthesis

autoinducer AI-1 biosynthesis

autoinducer AI-2 biosynthesis

autoinducer AI-2 biosynthesis II (Vibrio)

biphenyl degradation

chlorinated phenols degradation

chorismate biosynthesis from 3-dehydroquinate

cis-calamenene related sesquiterpenoids biosynthesis

CMP-2-keto-3-deoxy-D-glycero-D-galacto-nononate biosynthesis

CMP-N-acetylneuraminate biosynthesis I (eukaryotes)

CMP-N-acetylneuraminate biosynthesis II (bacteria)

CMP-N-glycoloylneuraminate biosynthesis

CMP-pseudaminate biosynthesis

creatine-phosphate biosynthesis

cysteine biosynthesis II (Archaea)

dolichol and dolichyl phosphate biosynthesis

flavin biosynthesis II (archaea)

flavin biosynthesis III (eukaryotes)

gentisate degradation

glycerol degradation II

glycerol degradation III

histamine biosynthesis

histamine degradation

lanosterol biosynthesis

methylsalicylate degradation

mevalonate pathway II (archaea)

salicylate degradation I

serine racemization

(S)-reticuline biosynthesis II

tetrahydromethanopterin biosynthesis

tyrosine biosynthesis IV

New Pathways from Plant Metabolic Network (PMN)

chrysoeriol biosynthesis

hydroxyjasmonate sulfate biosynthesis

indole-3-acetyl-amino acid biosynthesis

jasmonoyl-amino acid conjugates biosynthesis I

jasmonoyl-amino acid conjugates biosynthesis II

luteolin glycosides biosynthesis

quercetinsulphates biosynthesis

thiamine biosynthesis II

New Superpathways

alliin degradation

gluconeogenesis II (Methanobacterium thermoautotrophicum)

Methanobacterium thermoautotrophicum biosynthetic metabolism

superpathway of jasmonoyl amino acid biosynthesis

superpathway of salicylate degradation

superpathway of sialic acid and CMP-sialic acid biosynthesis

Updated Pathways

γ-hexachlorocyclohexane degradation

coenzyme B biosynthesis

glutamate biosynthesis V

glycine degradation (creatine biosynthesis)

IAA biosynthesis I

IAA conjugate biosynthesis II

pentachlorophenol degradation

removal of superoxide radicals

S-adenosyl-L-methionine cycle II (eukaryotic)

(S)-reticuline biosynthesis I

---

Release Notes for MetaCyc Version 13.0

Released on March 9, 2009

MetaCyc KB Statistics

Pathways	1289
Reactions	7686
Enzymes	5528
Chemical Compounds	7722
Organisms	1683
Citations	19155

 

The MetaCyc Web site has been redesigned to provide a new toolbar and new search commands. For quick instructions on how to use it, click here, or watch the webinar on how to use the new site.

New and Updated Pathways

We have added 92_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 17 pathways by adding commentary and updated enzyme and gene information, for a total of 109 new and updated pathways. Of the new pathways, 16 were contributed by PMN (Plant Metabolic Network) curators (www.plantcyc.org); four were contributed by MouseCyc (Mouse Genome Informatics) curator Alexei Evsikov (mousecyc.jax.org); two were contributed by the Rhodococcus Genome Project, Eltis laboratory (www.rhodococcus.ca); and one was contributed by SRI postdoctoral fellow Malabika Sarker.  We also added four new superpathways, one of which was contributed by PMN.

During this release we have significantly expanded our coverage of bacterial degradation pathways for chloro-aromatic compounds, important pollutants of the environment. Another field that received extensive curation concerns the metabolism of dimethylsulfide, the major contributor of sulfur to the atmosphere, and related compounds.  Other additions include new pathways for the biosynthesis of tyrosine, mannosylfructose, zymosterol, indican and indigo, as well as pathways for the degradation of pseudouridine, acetoin, citrate, 4-sulfocatechol, ethanedisulfonate, malonate, anthranilate, 4-ethylphenol and nitrilotriacetate.

A new pathway for mycolate biosynthesis in Mycobacterium tuberculosis H37Rv represents an important pathway for the design of anti-tubercular drugs.  Mycolic acids are components of the mycobacterial cell wall and are essential for survival of the organism.  They are responsible for the unusually low permeability and consequent resistance to common antibiotics, as well as for virulence and the persistence of the tubercle bacillus within infected organisms.  This pathway details the biosynthesis of mycolic acids and their processing into final products.

In animal metabolism, we added pathways for the biosynthesis of bile acids, 1,25-dihydroxyvitamin D3 and L-carnitine, as well as the mitochondrial L-carnitine shuttle pathway and a pathway for spermine and spermidine degradation.

In plant primary metabolism we focused our curation effort in the biosynthesis of ascorbate (vitamin C), various phospholipids, and the cell surface lipids cutin and wax. We created three new biosynthesis pathways for ascorbate, three for phosphatidylcholine, two for phosphatidylglycerol and one for phosphatidylethanolamine.  In addition, we updated five existing pathways for ascorbate, cutin, cuticular wax, glycolipid, and phospholipid biosynthesis.  We also continued our effort to further enhance the coverage of plant secondary metabolites with new pathways for the biosynthesis of vitexin, isovitexin, peonidin and their derivatives, flavonols, triterpenoids(one of which could be used as a source for potential hydrocarbon fuels), cinnamates and sterols.  We also added pathways for the biosynthesis of methylquercetin, the alkaloid capsiconiate, a  higher plant pathway for protein turnover in germinating seeds, and a plant pathway for 2,4,6-trinitrotoluene (TNT) degradation. In addition, we added two algal pathways for alginate biosynthesis.

We thank Dr. Carol Bult and Dr. Alexei Evsikov from the Jackson Laboratory for their contribution of pathways from the MouseCyc database (mousecyc.jax.org).

We thank Dr. Lindsay Eltis and Dr. Hao-Ping Chen from the University of British Columbia for their contribution of pathways from the Rhodococcus jostii RHA1 database (www.rhodococcus.ca).

We thank Malabika Sarker from SRI International for her contribution of the Mycobacterium tuberculosis mycolate biosynthesis pathway, by far the largest pathway in our database.

Other Improvements

Update of EC Reactions

During this quarter we have updated the reactions in MetaCyc with the latest information (as of January 2009) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by incorporating the final version of supplement 14 (see Enzyme Nomenclature Supplement 14).

Compound Protonation and Reaction Balancing

Starting with version 13.0, all MetaCyc compounds have been adjusted to a consistent protonation state for a reference pH of 7.3, common in the cellular cytosol. This adjustment was performed using the Marvin computational chemistry software (ChemAxon, Ltd). In addition, all reactions that had a mass-imbalance due only to hydrogen atoms were computationally balanced by adding or removing protons from the appropriate side of the reaction.

 These updated compounds and reactions will be propagated into all BioCyc PGDBs, and to other PGDBs created using Pathway Tools, making it easier to apply flux-balance analysis (FBA) techniques to these databases. This change results in certain differences between some MetaCyc reactions and the comparable reactions in other databases, such as the Enzyme Database . However, we believe that the representation of reactions in MetaCyc is more consistent and, within the limits of the cytosolic pH of 7.3, more accurate.

List of New and Updated Pathways

New Pathways

1,2,4,5-tetrachlorobenzene degradation

1,2,4-trichlorobenzene degradation

1,2-dichlorobenzene degradation

1,25-dihydroxyvitamin D₃ biosynthesis

1,3-dichlorobenzene degradation

2,4-dichlorophenoxyacetate degradation

3,4,6-trichlorocatechol degradation

3,4-dichlorocatechol degradation

3,5-dichlorocatechol degradation

3-chlorobenzoate degradation (aerobic)

3-chlorocatechol degradation

3-chlorotoluene degradation I

3-chlorotoluene degradation II

4-chloro-2-methylphenoxyacetate degradation

4-chlorocatechol degradation

4-ethylphenol degradation (anaerobic)

4-sulfocatechol degradation

5-chloro-3-methyl-catechol degradation

acetoin degradation

alginate biosynthesis I

alginate biosynthesis II

anthranilate degradation I (aerobic)

anthranilate degradation II (aerobic)

avenacin biosynthesis

bile acid biosynthesis, neutral pathway

C30 botryococcene biosynthesis

capsiconiate biosynthesis

cardenolide biosynthesis

cardenolide glucosides biosynthesis

ceramide biosynthesis

chlorobenzene degradation

chlorogenic acid biosynthesis II

chlorogenic acid biosynthesis I

chlorosalicylate degradation

citrate degradation

dammara-18(28),21-diene biosynthesis

dimethylsulfide degradation I

dimethylsulfide degradation II (oxidation)

dimethylsulfide degradation III (oxidation)

dimethylsulfone degradation

dimethylsulfoniopropionate biosynthesis I (Wollastonia)

dimethylsulfoniopropionate biosynthesis II (Spartina)

dimethylsulfoniopropionate biosynthesis III (algae)

dimethylsulfoniopropionate degradation I (cleavage)

dimethylsulfoniopropionate degradation II (cleavage)

dimethylsulfoniopropionate degradation III (demethylation)

dimethylsulfoxide degradation

diploterol and cycloartenol biosynthesis

ethanedisulfonate degradation

glycerol-3-phosphate shuttle

indican biosynthesis

indigo biosynthesis

L-carnitine biosynthesis

malonate degradation II (biotin-dependent)

mangrove triterpenoid biosynthesis

mannosylfructose biosynthesis

methanesulfonate degradation

methylthiopropionate degradation I (cleavage)

methylthiopropionate degradation II (demethylation)

mitochondrial L-carnitine shuttle pathway

mycolate biosynthesis

nitrilotriacetate degradation

pseudoeuridine degradation

seed germination protein turnover

serotonin and melatonin biosynthesis

spermine and spermidine degradation

sphingomyelin metabolism

sphingosine and sphingosine-1-phosphate metabolism

tyrosine biosynthesis III

zymosterol biosynthesis

New Pathways from Plant Metabolic Network (PMN)

2,3-cis-flavanols biosynthesis

2,3-trans-flavanols biosynthesis

2,4,6-trinitrotoluene degradation

ascorbate biosynthesis II (L-gulose pathway)

ascorbate biosynthesis III (VTC2 cycle)

ascorbate biosynthesis IV (extended VTC2 cycle)

isovitexin and isovitexin glycosides biosynthesis

methylquercetin biosynthesis

peonidin and derivatives biosynthesis

phosphatidylcholine biosynthesis II

phosphatidylcholine biosynthesis III

phosphatidylcholine biosynthesis IV

phosphatidylglycerol biosynthesis I

phosphatidylglycerol biosynthesis II

phosphatidylethanolamine biosynthesis II

vitexin and detivatives biosynthesis

New Pathways from MouseCyc

ceramide biosynthesis

serotonin and melatonin biosynthesis

sphingomyelin metabolism

sphingosine and sphingosine-1-phosphate metabolism

New Pathways from the Rhodococcus jostii RHA1 database

biphenyl degradation

phthalate degradation

New Superpathways

superpathway of dimethylsulfone degradation

superpathway of dimethylsulfoniopropionate degradation

superpathway of mycolate biosynthesis

superpathway of phosphatidylcholine biosynthesis

Updated Pathways

1,4-dichlorobenzene degradation

ascorbate biosynthesis I (galactose pathway)

ascorbate biosynthesis VI

cuticular wax biosynthesis

cutin biosynthesis

ergosterol biosynthesis

ethylbenzene degradation (anaerobic)

glycolipid biosynthesis

histidine biosynthesis

lupeol biosynthesis

malonate degradation I (biotin-independent)

phospholipid biosynthesis II

proanthocyanidin biosynthesis from flavanols

superpathway of ergosterol biosynthesis

thiamin biosynthesis I

tyrosine biosynthesis II

uridine-5'-phosphate biosynthesis

---

Release Notes for MetaCyc Version 12.5

Released on October 15, 2008

MetaCyc KB Statistics

Pathways	1203
Reactions	7312
Enzymes	5127
Chemical Compounds	7234
Organisms	1549
Citations	17916

New and Updated Pathways

We have added 72_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised seven pathways by adding commentary and updated enzyme and gene information, for a total of 79 new and updated pathways. Of the new pathways, 12 were contributed by PMN (Plant Metabolic Network) curators (http://plantcyc.org), two were contributed by SGD (Saccharomyces Genome Database) curator Cynthia Krieger (http://pathway.yeastgenome.org/biocyc/) and 13 were imported from EcoCyc, as shown below.  We also added three new superpathways.  The superpathway of linamarin and lotaustralin biosynthesis was also contributed by PMN.

During this period we have significantly revised our coverage of fatty acid biosynthesis. Detailed pathways now describe the biosynthesis of the basic long chain saturated fatty acids palmitate and stearate.  Additional pathways cover the biosynthesis of common unsaturated fatty acids such as palmitoleate, cis-vaccenate, oleate, linoleate, α-linolenate and γ-linolenate. Other additions include new pathways for the biosynthesis of trehalose, acetoin, L-asparagine, butanediol, CDP-diacylglycerol, glycine betaine, and molybdopterin guanine dinucleotide.  We also added pathways for the degradation of sulfoacetaldehyde, and nitrate assimilation in cyanobacteria.  In the area of microbial secondary metabolism we added pathways for the biosynthesis of aflatoxins, geosmin, and the antibiotics rifamycin B and gramicidin S.

In plant metabolism, we continued to focus on further enhancing our coverage of plant secondary metabolites.  New pathways were added for the biosynthesis of the triterpenoids thalianal, marneral, baruol and arabidiol; the flavone apigenin; the sorghum allelochemical compound sorgoleone; the flavor and aroma-related compounds furaneol and cinnamate esters; and acridone alkaloids which are potential chemopreventive agents.  We also added pathways for the degradation of the cyanogenic glycosides lotasutraline, amygdalin and prunasin; and dhurrin degradation which involves hydrolysis of cyanogenic glucosides.  In primary metabolism, we curated pathways for the biosynthesis of xylogalacturonan - a pectic polysaccharide; the unusual fatty acids crepenynic acid and vernolic acid; the metal ion chelator nicotianamine; and lupinate which may stabilize plant hormone metabolism.  We also added a plant wound healing and defense pathway involving wound-induced proteolysis.  In addition we curated two transport pathways, one involving long distance transport of nicotianamine (NA) and one involving transport of ammonia for metabolic processes.

Other Improvements

Update of EC Reactions

During this quarter we have updated the reactions in MetaCyc with the latest information (as of August 2008) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by incorporating supplement 14 (see Enzyme Nomenclature Supplement 14).

List of New and Updated Pathways

New Pathways

α-linolenate biosynthesis

γ-linolenate biosynthesis I (plants)

γ-linolenate biosynthesis II (animals)

(1'S,5'S)-averufin biosynthesis

3-amino-5-hydroxybenzoate biosynthesis

cis-vaccenate biosynthesis

acetoin biosynthesis II

acridone alkaloid biosynthesis

acyl carrier protein metabolism

aflatoxins B₁ and G₁ biosynthesis

aflatoxins B₂ and G₂ biosynthesis

ammonium transport

asparaginyl-tRNA^asn biosynthesis via transamidation

butanediol biosynthesis

CDP-diacylglycerol biosynthesis III

cinnamate esters biosynthesis

dhurrin degradation

fatty acid biosynthesis initiation II

fatty acid biosynthesis initiation III

fatty acids biosynthesis (yeast)

Fe(II)-NA phloem transport

furaneol biosynthesis

geosmin biosynthesis

glycine betaine biosynthesis V (from glycine)

gramicidin S biosynthesis

kanosamine biosynthesis

linoleate biosynthesis I (plants)

linoleate biosynthesis II (animals)

lupinate biosynthesis

molybdenum cofactor (sulfide) biosynthesis

molybdopterin guanine dinucleotide biosynthesis

nicotianamine biosynthesis

nitrate reduction VI (assimilatory)

oleate biosynthesis II (animals)

palmitate biosynthesis I (animals)

palmitate biosynthesis II (bacteria and plants)

rifamycin B biosynthesis

stearate biosynthesis I (animals)

stearate biosynthesis II (plants)

sterigmatocystin biosynthesis

sulfoacetaldehyde degradation II

trehalose biosynthesis VI

trehalose biosynthesis VII

versicolorin B biosynthesis

wound-induced proteolysis

New Pathways from PMN (http://plantcyc.org)

amygdalin and prunasin degradation

apigenin glycosides biosynthesis

arabidiol biosynthesis

baruol biosynthesis

crepenynic acid biosynthesis

lotaustralin biosynthesis

lotaustralin degradation

marneral biosynthesis

sorgoleone biosynthesis

thalianol and derivatives biosynthesis

vernolic acid biosynthesis

xylogalacturonan biosynthesis

New Pathways from EcoCyc

biosynthesis of 4-amino-4-deoxy-L-arabinose-modified lipid A

formate to dimethyl sulfoxide electron transfer

formate to nitrate electron transfer

formate to trimethylamine N-oxide electron transfer

NADH to cytochrome bd oxidase electron transfer

NADH to cytochrome bo oxidase electron transfer

NADH to dimethyl sulfoxide reductase electron transfer

NADH to fumarate electron transfer

NADH to nitrate reductase electron transfer

NADH to trimethylamine N-oxide reductase electron transfer

oleate β-oxidation

succinate to cytochrome bd oxidase electron transfer

succinate to cytochrome bo oxidase electron transfer

New Pathways from SGD (http://pathway.yeastgenome.org/biocyc/)

acetoin biosynthesis III

butanediol degradation

New Superpathways

superpathway of aflatoxin biosynthesis

superpathway of rifamycin B biosynthesis

superpathway of linamarin and lotaustralin biosynthesis

Updated Pathways

fatty acid biosynthesis initiation I

petroselinate biosynthesis

palmitoleate biosynthesis

CDP-diacylglycerol biosynthesis I

CDP-diacylglycerol biosynthesis II

oleate biosynthesis I (plants)

superpathway of fatty acid biosynthesis II (plant)

---

Release Notes for MetaCyc Version 12.1

Released on June 27, 2008

MetaCyc KB Statistics

Pathways	1138
Reactions	7114
Enzymes	4986
Chemical Compounds	7140
Organisms	1505
Citations	17340

New and Updated Pathways

We have added 101_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 13 pathways by adding commentary and updated enzyme and gene information, for a total of 114 new and updated pathways. The N-acetylneuraminate and N-acetylmannosamine degradation pathway was imported from EcoCyc. We also created 20 new superpathways.

We have undertaken a major effort to enhance the curation of quinone biosynthesis to cover the different varieties of quinones found in prokaryotic and eukaryotic organisms. These include menaquinones, demethylmenaquinones and ubiquinones of different tail length, phylloquinone, plastoquinone and rhodoquinones, as well as the plant quinones alizarin, lawsone and juglone.

We also covered the microbial biosynthesis of CDP-3,6-dideoxyhexoses CDP-abequose, CDP-ascarylose, CDP-paratose and CDP-tyvelose which are important O-antigens of several enterobacterial species. In the area of microbial secondary metabolism, we added pathways for the biosynthesis of staphyloxanthin, tuberculosinol and the antibiotics albaflavenone, puromycin, streptomycin, terpentecin and validamycin A.

In plant metabolism we continue to expand our coverage of secondary metabolite biosynthesis including alkaloids, quinones (see above), terpenoids and isoflavonoid glycosides. We have added pathways for the biosynthesis of metabolites significant in plant defense such as maysin. We also added pathways of medical significance, including the biosynthesis of cocaine, quinine, hyperforin, hypericin and colchicine. Newly added pathways of industrial significance included rubber, urushiol and various scent volatiles. Pathways of primary metabolism include the biosynthesis of plant cell wall polysaccharides such as xylan and xyloglucan, several auxin metabolism pathways and biosynthetic pathways for wax esters, hypusine and homospermidine. We also curated two pathways involved in the production of phytosiderophores, as well as pathways involving iron chelation and transport.

List of New and Updated Pathways

New Pathways

(-)-(4S)-limonene degradation

(+)-(4R)-limonene degradation

(4R)-carveol and (4R)-dihydrocarveol degradation

(4R)-carvone biosynthesis

(4S)-carveol and (4S)-dihydrocarveol degradation

1,4-dihydroxy-2-naphthoate biosynthesis I

1,4-dihydroxy-2-naphthoate biosynthesis II (plants)

2'-(5'-phosphoribosyl)-3'-dephospho-CoA biosynthesis II (malonate decarboxylase)

2,3-dihydroxybenzoate biosynthesis

2'-deoxymugineic acid phytosiderophore biosynthesis

2-keto-L-gulonate biosynthesis

3-hydroxypropionate/4-hydroxybutyrate cycle

4-hydroxyphenylpyruvate biosynthesis

afrormosin conjugates interconversion

albaflavenone biosynthesis

alizarin biosynthesis

all-trans undecaprenyl diphosphate biosynthesis

beta-carboline biosynthesis

bornyl diphosphate biosynthesis

CDP-3,6-dideoxyhexose biosynthesis

CDP-abequose biosynthesis

CDP-ascarylose biosynthesis

CDP-paratose biosynthesis

CDP-tyvelose biosynthesis

cinchona alkaloids biosynthesis

cocaine biosynthesis

colchicine biosynthesis

dalcochinin biosynthesis

dalpatein and dalnigrein biosynthesis

decaprenyl diphosphate biosynthesis

demethylmenaquinone-6 biosynthesis

demethylmenaquinone-8 biosynthesis

demethylmenaquinone-9 biosynthesis

dodecaprenyl diphosphate biosynthesis

ephedrine biosynthesis

epoxypseudoisoeugenol-2-methylbutyrate biosynthesis

eugenol and isoeugenol biosynthesis

Fe(III)-phytosiderophore transport

Fe(III)-reduction and Fe(II) transport

geraniol and geranial biosynthesis

geranyl acetate biosynthesis

glutaminyl-tRNA^gln biosynthesis via transamidation

heliocides biosynthesis

heme degradation

heptaprenyl diphosphate biosynthesis

homospermidine biosynthesis

hydroxylated mugineic acid phytosiderophore biosynthesis

hyperforin biosynthesis

hypericin biosynthesis

hypoglycin biosynthesis

hypusine biosynthesis

IAA conjugate biosynthesis III

IAA degradation V

IAA degradation VI

IAA degradation VII

juglone biosynthesis

lacinilene C biosynthesis

lawsone biosynthesis

linear furonocoumarin biosynthesis II

magnoflorine biosynthesis

malonate degradation

maysin biosynthesis

menaquinone-10 biosynthesis

menaquinone-11 biosynthesis

menaquinone-12 biosynthesis

menaquinone-13 biosynthesis

menaquinone-6 biosynthesis

menaquinone-7 biosynthesis

menaquinone-9 biosynthesis

N-acetylneuraminate and N-acetylmannosamine degradation

nonaprenyl diphosphate biosynthesis

octaprenyl diphosphate biosynthesis

oligomeric urushiol biosynthesis

phycocyanobilin biosynthesis

phycoerythrobilin biosynthesis

puromycin biosynthesis

rhodoquinone-10 biosynthesis

rhodoquinone-9 biosynthesis

rubber biosynthesis

simple coumarins biosynthesis

staphyloxanthin biosynthesis

streptomycin biosynthesis

t-anethole biosynthesis

TCA cycle variation IV

terpentecin biosynthesis

trichloroethylene degradation

tridecaprenyl diphosphate biosynthesis

tuberculosinol biosynthesis

ubiquinone-10 biosynthesis (eukaryotic)

ubiquinone-10 biosynthesis (prokaryotic)

ubiquinone-7 biosynthesis (eukaryotic)

ubiquinone-7 biosynthesis (prokaryotic)

ubiquinone-8 biosynthesis (eukaryotic)

ubiquinone-9 biosynthesis (eukaryotic)

ubiquinone-9 biosynthesis (prokaryotic)

usnate biosynthesis

validamycin A biosynthesis

wax esters biosynthesis I

wax esters biosynthesis II

xylan biosynthesis

xyloglucan biosynthesis

New Superpathways

bacillibactin biosynthesis

butanediol biosynthesis I

butanediol biosynthesis II

heme biosynthesis I

heme biosynthesis II

superpathway of carotenoid biosynthesis

superpathway of CDP-3,6-dideoxyhexose biosynthesis

superpathway of demethylmenaquinone-6 biosynthesis

superpathway of demethylmenaquinone-8 biosynthesis

superpathway of demethylmenaquinone-9 biosynthesis

superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate)

superpathway of menaquinone-10 biosynthesis

superpathway of menaquinone-11 biosynthesis

superpathway of menaquinone-12 biosynthesis

superpathway of menaquinone-13 biosynthesis

superpathway of menaquinone-6 biosynthesis

superpathway of menaquinone-7 biosynthesis

superpathway of menaquinone-8 biosynthesis

superpathway of phylloquinone biosynthesis

superpathway of plastoquinone biosynthesis

Updated Pathways

1,4-dihydroxy-2-naphthoate biosynthesis II (plants)

2'-(5''-phosphoribosyl)-3'-dephospho-CoA biosynthesis I (citrate lyase)

calystegine biosynthesis

de novo biosynthesis of pyrimidine deoxyribonucleotedes

enterobactin biosynthesis

geranylgeranyldiphosphate biosynthesis

IAA degradation IV

NAD biosynthesis III

photosynthesis, light reactions

plastoquinone biosynthesis

sanguinarine and macarpine biosynthesis

secologanin and strictosidine biosynthesis

superpathway of geranylgeranyldiphosphate biosynthesis II (via MEP)

 

---

Release Notes for MetaCyc Version 12.0

Released on April 1, 2008

MetaCyc KB Statistics

Pathways	1036
Reactions	6739
Enzymes	4731
Chemical Compounds	6719
Organisms	1108
Citations	16335

New and Updated Pathways

We have added 51_{[more info]} new pathways to MetaCyc since the last release.  In addition, we significantly revised 15 pathways by adding commentary and updated enzyme and gene information, for a total of 66 new and updated pathways.

Among the new microbial pathways curated in MetaCyc during the last quarter are a newly discovered autotrophic CO₂ fixation pathway (comprising the 3-hydroxypropionate cycle and glyoxylate assimilation pathway), several pathways for the degradation of s-triazine herbicides such as atrazine, the biosynthesis of several GDP-sugars, and the biosynthesis and degradation pathways of itaconate.  In the area of antibiotic biosynthesis we added a pathway for (5R)-carbapenem which is a member of the carbapenem class of beta-lactam antibiotics, and pathways for the biosynthesis of fosfomycin and the phenazine compounds phenazine-1-carboxylate and 2-hydroxyphenazine.  We also added a CDP-diacylglycerol biosynthesis pathway from EcoCyc, and created a superpathway of atrazine degradation..

We also added a pathway for 4-hydroxybenzoate biosynthesis in higher and lower eukaryotes.  In addition, we  imported 9 new pathways from YeastCyc (part of the Saccharomyces Genome Database) that describe pathways found in that organism.

In plant metabolism we curated a variety of new pathways for the biosynthesis of plant secondary metabolites.  These include:  the sesquiterpenoids farnesene, germacrene and costunolide; the toxic terpenoid gossypol found in cotton; three triterpene saponin glycosylation pathways; the alkaloids capsaicin, hemlock poisons gamma-coniciene and coniine, and piperine (which gives black pepper its pungent flavor); rotenoid; and the isoflavans vestitol and sativan.  We also added a superpathway of formononetin derivative biosynthesis showing the formation of two of the many isoflavonoids derived from this compound, as well as the production of a storage form of formononetin.  In general these plant secondary metabolites are involved in plant defense and/or stress responses and many have potential applications in medicine and agriculture.  Also in the area of plant secondary metabolism we curated new pathways for the degradation of ethiin, alliin and isoalliin, and we updated the pathway for hyoscyamine and scopolamine biosynthesis.

In addition, we curated biosynthetic pathways for the plant scent volatiles phenylethanol and trimethoxybenzene.  In the area of plant energy metabolism we added a pathway for the Rubisco shunt, a bypass of glycolysis providing an efficient way for plants to convert carbohydrates into seed storage oil.

Other Improvements

Update of EC Reactions

During this quarter we have updated the reactions in MetaCyc with the latest information (as of January 2008) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by  incorporating supplement 13 (see Enzyme Nomenclature Supplement 13).

We would like to welcome a new curator,  Dr. A. Karthikeyan (Karthik) from the Carnegie Institution, to the MetaCyc team.

List of New and Updated Pathways

New Pathways

β-alanine biosynthesis V

γ-coniciene and coniine biosynthesis

(5R)-carbapenem biosynthesis

1,3,5-trimethoxybenzene biosynthesis

2-hydroxyphenazine biosynthesis

2-methylcitrate cycle II

3-hydroxypropionate cycle

4-hydroxybenzoate biosynthesis I (eukaryotes)

4-hydroxybenzoate biosynthesis II

alliin degradation

atrazine degradation II

atrazine degradation III

capsaicin biosynthesis

costunolide biosynthesis

deethylsimazine degradation

ethiin degradation

ethylmalonyl pathway

farnesene biosynthesis

fosfomycin biosynthesis

GDP-α-D-perosamine biosynthesis

GDP-6-deoxy-D-talose biosynthesis

GDP-L-colitose biosynthesis

germacrene biosynthesis

glutamate degradation X

glycogen degradation II

glyoxylate assimilation

gossypol biosynthesis

isoalliin degradation

isopropylamine degradation

itaconate biosynthesis

itaconate degradation

phenazine-1-carboxylate biosynthesis

phenylethanol biosynthesis

piperine biosynthesis

pyruvate fermentation to acetate VIII

rotenoid biosynthesis

Rubisco shunt

saponin biosynthesis II

saponin biosynthesis III

saponin biosynthesis IV

vestitol and sativan biosynthesis

Imported Pathways

4-aminobutyrate degradation III

4-hydroxybenzoate biosynthesis III (yeast)

CDP-diacylglycerol biosynthesis I

glycine biosynthesis III

glycine biosynthesis IV

hexaprenyl diphosphate biosynthesis

NAD salvage pathway III

phosphatidylcholine biosynthesis

tyrosine degradation III

ubiquinone-6 biosynthesis

Superpathways

superpathway of atrazine degradation

Superpathway of formononetin derivative biosynthesis

Updated Pathways

2-methylcitrate cycle I

4-aminobutyrate degradation III

arginine degradation IX (arginine:pyruvate transaminase pathway)

arginine degradation IX (arginine:pyruvate transaminase pathway)

atrazine degradation I (aerobic)

cyanurate degradation

glycine biosynthesis I

glyoxylate cycle

hexaprenyl diphosphate biosynthesis

hyoscyamine and scopolamine biosynthesis

nicotinate degradation III

peptidoglycan biosynthesis I

polyisoprenoid biosynthesis (E. coli)

tyrosine degradation III

ubiquinone-6 biosynthesis

---

Release Notes for MetaCyc Version 11.6

Released on December 5, 2007

MetaCyc KB Statistics

Pathways	1010
Reactions	6576
Enzymes	4582
Chemical Compounds	6561
Organisms	1077
Citations	15875

New and Updated Pathways

79 new pathways (including one superpathway) were added to MetaCyc since the last release. In addition, we significantly revised 30 pathways, by adding commentary and updated enzyme and gene information, for a total of 109 new and updated pathways.

Major additions include a much better coverage for the microbial degradation of nitroaromatic compounds, urate and allantoin metabolism, and acetate metabolism. We have added pathways for the biosynthesis of bacteriochlorophyll a, several GDP-sugars, the compatible solutes glucosyl- and mannosyl-glycerate, the enzyme cofactor tetrahydrobiopterin, and several naturally occurring β-lactam antibiotics, including the penam, ceph-3-em and clavam classes. We also significantly enhanced coverage of nitrate reduction, and added pathways for propylene degradation, sorbitol biosynthesis, and many other miscellaneous pathways.

In plant metabolism we curated six new secondary metabolic pathways. The new pathways include biosynthesis of the fragrance compound linalool and the flavor compounds of vanilla, garlic, onion and chive, biosynthesis of the toxic metabolites α-solanine and α-chaconine, which are found in potatoes, and biosynthesis of two terpenoid drugs: the important anticancer drug taxol, which is produced in yew trees, and the multi-use drug ginseng.

We would like to welcome new members to the MetaCyc team: Drs. Lukas Mueller and Anuradha Pujar from Cornell University, and Dr. Kate Dreher from the Carnegie Institution.

New Pathways

2,4-dinitrotoluene degradation

2,6-dinitrotoluene degradation

2-nitrobenzoate degradation I

2-nitrobenzoate degradation II

2-nitrophenol degradation

2-nitrotoluene degradation

4-chloronitrobenzene degradation

4-nitrotoluene degradation II

acetate conversion to acetyl-CoA

acetate formation from acetyl-CoA I

acetate formation from acetyl-CoA II

acetate formation from acetyl-CoA III (succinate)

acetone degradation II (to acetoacetate)

acetyl-CoA fermentation to butyrate II

adenosine 5'-monophosphate recycling

allantoin degradation to glyoxylate I

allantoin degradation to glyoxylate II

allantoin degradation to glyoxylate III

bacteriochlorophyll a biosynthesis

cardiolipin biosynthesis I

cephalosporin C biosynthesis

cephamycin C biosynthesis

chlorophyllide a biosynthesis II

clavulanate biosynthesis

CO₂ fixation into oxaloacetate

de novo biosynthesis of uridine-5'-monophosphate

deacetylcephalosporin C biosynthesis

epoxysqualene biosynthesis

fructose degradation

GDP-glucose biosynthesis

GDP-mannose biosynthesis I

GDP-mannose biosynthesis II

ginsenoside biosynthesis

glucosylglycerate biosynthesis

isopenicillin N biosynthesis

linalool biosynthesis

L-lactaldehyde degradation (aerobic)

L-lactaldehyde degradation (anaerobic)

mannosylglycerate biosynthesis I

mannosylglycerate biosynthesis II

nitrate reduction III (dissimilatory)

nitrate reduction IV (dissimilatory)

nitrate reduction V (assimilatory)

nitrobenzene degradation I

nitrobenzene degradation II

penicillin K biosynthesis

phosphatidyl-ethanolamine biosynthesis

propylene degradation

pyrimidine ribonucleotides interconversion

pyruvate fermentation to acetate V

pyruvate fermentation to acetate VI

pyruvate fermentation to acetate VII

shikonin biosynthesis

sorbitol biosynthesis II

steroidal glycoalkaloid biosynthesis

succinate fermentation to butyrate

sulfolipid biosynthesis

taxol biosynthesis

TCA cycle variation III (higher eukaryotes)

tetrahydrobioprein biosynthesis I

tetrahydrobioprein biosynthesis II

tryptophan degradation IX

urate biosynthesis

urate degradation to allantoin

urea degradation I

urea degradation II

vanilla biosynthesis

Superpathways

superpathway of penicillin, cephalosporin and cephamycin biosynthesis

Updated Pathways

4-nitrobenzoate degradation

4-nitrotoluene degradation I

4-toluenecarboxylate degradation

4-toluenesulfonate degradation I

acetyl-CoA fermentation to butyrate II

acetylene degradation

cardiolipin biosynthesis II

chlorophyll cycle

chlorophyllide a biosynthesis I

de novo biosynthesis of pyrimidine ribonucleotides

fatty acid β-oxidation IV (plant, unsaturated, even number)

fatty acid activation

glutamate degradation V (via hydroxyglutarate)

incomplete reductive TCA cycle

methionine biosynthesis I

methionine salvage pathway

NAD/NADH phosphorylation and dephosphorylation

nitrate reduction I (denitrification)

octane oxidation

superpathway of allantoin degradation (E. coli)

superpathway of allantoin degradation in plants

superpathway of allantoin degradation in yeast

superpathway of C1 compounds oxidation to CO₂

superpathway of purines degradation in plants

superpathway of sulfur amino acid biosynthesis (Saccharomyces cerevisiae)

taurine biosynthesis

thiocyanate degradation I

thiocyanate degradation II

ureide biosynthesis

very long chain fatty acid biosynthesis

---

Release Notes for MetaCyc Version 11.5

Released on August 15, 2007

MetaCyc KB Statistics

Pathways	977
Reactions	6483
Enzymes	4332
Chemical Compounds	6375
Organisms	1029
Citations	15199

New and Updated Pathways

10 new pathways were added to MetaCyc since the last release. In addition, we significantly revised 5 pathways, by adding commentary and updated enzyme and gene information, for a total of 15 new and updated pathways.

In microbial metabolism we curated 7 new pathways, incorporated one new pathway from EcoCyc, and significantly enhanced 5 existing pathways, for a total of 13 pathways.

We have updated our coverage of the biosynthesis of adenosylcobalamin (vitamin B12), one of the most structurally complex small molecules made in nature. MetaCyc pathways describe both the aerobic and anaerobic biosynthetic routes, and the synthesis of one of its precursors, 5,6-dimethylbenzimidazole (DMB). We also added a pathway for biosynthesis of the important vitamin L-ascorbate (vitamin C) in bacteria, a pathway for the biosynthesis of the amino sugar donor UDP-N-acetyl-D-galactosamine, and pathways for degradation of the pentose sugars arabinose and xylose.

In mammalian metabolism we curated two new pathways: a pathway for biosynthesis of L-ascorbate (vitamin C) in higher animals, and a pathway for degradation of the sugar acid glucuronate.

New Microbial Pathways

5,6-dimethylbenzimidazole biosynthesis

L-ascorbate biosynthesis II

D-arabinose degradation III

L-arabinose degradation II

L-arabinose degradation III

UDP-N-acetyl-D-galactosamine biosynthesis II

xylose degradation II

A New Microbial Pathway from EcoCyc

chitobiose degradation

New Mammalian Pathways

L-ascorbate biosynthesis III

glucuronate degradation

Updated Microbial Pathways

adenosylcobalamin biosynthesis I (early cobalt insertion)

adenosylcobalamin biosynthesis II (late cobalt incorporation)

adenosylcobalamin salvage from cobinamide and cobalamin

xylitol degradation

Superpathway of pentose and pentitol degradation

---

Release Notes for MetaCyc Version 11.1

Released on May 25, 2007

MetaCyc KB Statistics

Pathways	966
Reactions	6464
Enzymes	4271
Chemical Compounds	6354
Organisms	1023
Citations	14937

New and Updated Pathways

39 new pathways were added to MetaCyc since the last release. In addition, we significantly revised 31 pathways, by adding commentary and updated enzyme and gene information. We also created 1 new superpathway, for a total of 71 new and updated pathways.

In microbial metabolism we curated 20 new pathways, incorporated 6 new EcoCyc pathways, and significantly enhanced 31 existing pathways, for a total of 57 pathways.

Several topics received special attention during this release. We have reorganized and significantly expanded our coverage of fermentation pathways, the metabolism of the amino acids glutamate, glutamine, aspartate and asparagine, the degradation of the pesticide parathion and related compounds, and the metabolism of the vitamins B6 and B12. In addition we added or revised many pathways covering a wide range of topics, including purine degradation, the reductive monocarboxylate cycle, and polyhydroxybutyrate biosynthesis, to name a few.

In plant metabolism we added 13 new pathways and one superpathway.  Five well-known alkaloid biosynthesis pathways complete the coverage of this domain. In addition, we added two biosynthetic pathways of hydroxycinnamic acid amides. The serotonin amides are reported to be antioxidants, and the tyramine amides, widespread in plants, are cell wall constituents playing a role in cell wall reinforcement and protection of plants against pathogen infections. Finally, we curated six new  pathways for the biosynthesis of phenylpropenoids belonging to the class of lignans and hydrolyzable tannins, a group of compounds reported to have, amongst other things, antioxidant and antitumor properties.  A superpathway of hydrolyzable tannins was also created.

Special thanks: We bid a fond farewell to our colleagues Drs. Sue Rhee, Peifen Zhang, Hartmut Foerster, and Chris Tissier of the Carnegie Institution. The Carnegie group has curated a large number of plant pathways and enzymes into MetaCyc, making it the most comprehensive existing database on plant metabolism.  Thank you for your many contributions to MetaCyc, and to the curation procedures and software behind it.

New Microbial Pathways

adenosylcobalamin biosynthesis from cobyrinate a,c-diamide I

adenosylcobalamin biosynthesis from cobyrinate a,c-diamide II

adenosylcobalamin biosynthesis I (early cobalt insertion)

diethylphosphate degradation

glycolysis V

methanol oxidation to formaldehyde

methyl parathion degradation

p-nitrophenol degradation I

p-nitrophenol degradation II

paraoxon degradation

purine degradation II (anaerobic)

pyruvate fermentation to acetate II

pyruvate fermentation to acetate III

pyruvate fermentation to acetate IV

pyruvate fermentation to ethanol I

pyruvate fermentation to ethanol II

pyruvate fermentation to lactate

pyruvate fermentation to propionate II (acrylate pathway)

reductive monocarboxylic acid cycle

UDP-N-acetyl-D-galactosamine biosynthesis

New Microbial Pathways from EcoCyc

2-O-α-mannosyl-D-glycerate degradation

aminopropylcadaverine biosynthesis

arginine dependent acid resistance

glutamate dependent acid resistance

L-galactonate degradation

melibiose degradation

Updated Microbial Pathways

adenosylcobalamin biosynthesis II (late cobalt incorporation)

asparagine biosynthesis I

asparagine degradation I

aspartate biosynthesis

aspartate degradation I

aspartate degradation II

Bifidobacterium shunt

cyclohexanol degradation

formaldehyde assimilation III (dihydroxyacetone cycle)

glutamate biosynthesis II

glutamate biosynthesis IV

glutamine biosynthesis I

glutamine degradation I

glutamine degradation II

glycine biosynthesis II

glycine cleavage complex

heterolactic fermentation I

hexitol fermentation to lactate, formate, ethanol and acetate

homolactic fermentation

L-alanine fermentation to propionate and acetate

methionine biosynthesis I

N-acetylneuraminate degradation

parathion degradation

polyhydroxybutyrate biosynthesis

purine degradation III (anaerobic)

pyruvate fermentation to acetate I

pyruvate fermentation to propionate I

reductive acetyl coenzyme A pathway

superpathway of glutamate and glutamine biosynthesis

UDP-N-acetyl-D-glucosamine biosynthesis II

vitamin B₆ degradation

New Plant Pathways

bisbenzylisoquinoline alkaloid biosynthesis

cornusiin E biosynthesis

gallotannin biosynthesis

gramine biosynthesis

hydroxycinnamic acid serotonin amides biosynthesis

hydroxycinnamic acid tyramine amides biosynthesis

laudanine biosynthesis

lupanine biosynthesis

matairesinol biosynthesis

palmatine biosynthesis

pentagalloylglucose biosynthesis

podophyllotoxin and 6-methoxypodophyllotoxin biosynthesis

sesamin biosynthesis

New Superpathways

superpathway of hydrolyzable tannin biosynthesis

---

Release Notes for MetaCyc Version 11.0

Released on March 16, 2007

MetaCyc KB Statistics

Pathways	935
Reactions	6262
Enzymes	3995
Chemical Compounds	6218
Organisms	952
Citations	12729

New and Updated Pathways

47 new pathways were added to MetaCyc since the last release. In addition, we significantly revised 26 pathways, by adding commentary and updated enzyme and gene information. We also created 12 new superpathways, for a total of 85 new and updated pathways.

In microbial metabolism we curated 16 new pathways, incorporated 4 new EcoCyc pathways and one ScoCyc pathway, and significantly enhanced 20 existing pathways, for a total of 41 pathways.

Topics that were covered include the metabolism of the toxic compounds methylglyoxal and phenylmercury acetate, the degradation of the amino acids alanine and threonine, and the degradation of miscellaneous aromatic and non-aromatic compounds including phenol, benzene, catechol, toluene, naphthalene, xylene, acrylonitrile, 4-hydroxyphenylacetate, and acetone. We also modified several pathways of sugar metabolism. In addition, we incorporated 4 new pathways from EcoCyc, describing the degradation of purine and pyrimidine nucleosides, and a Streptomyces coelicolor A3(2) pathway for the biosynthesis of the polyketide antibiotic actinorhodin, which was submitted by Veronica Armendarez of the  John Innes Centre. Thank you Veronica!

In plant metabolism we added 26 new pathways, and enhanced 6 pathways, for a total of 32 pathways.

A special focus was given to the metabolism of betalains, which constitute chromo-alkaloid pigments that replace anthocyanins in the plant order Caryophyllales.  The lipoxygenase (LOX) pathway, which leads to the biosynthesis of a wide variety of compounds such as jasmonic acid, volatile aldehydes and alcohols, alpha ketols, and divinyl ethers, has been extensively overhauled. MetaCyc now contains the 9-LOX, 13-LOX and their corresponding AOS (allene oxide synthase), HPL (hydroperoxide lyase) and DES (divinyl ether synthase) branches curated in separate pathways.  An exhaustive list of pathways involved in the biosynthesis of oleoresin compounds found in coniferous plants have been added to the database.  Finally, a number of new pathways concerning various compound classes, such as terpenoids (DMNT and crocetin biosynthesis) have also been added.

We have also extensively updated pathways relating to glycolysis and related pathways (starch biosynthesis and TCA cycle) in plants by adding a comprehensive list of cytosolic and plastidic enzymes, as well as pathways concerning homomethonine and jasmonic acid biosynthesis.

Update of EC Reactions

During this quarter we have updated the reactions in MetaCyc with the latest information (as of January 2007) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by  incorporating supplement 12 (see Enzyme Nomenclature Supplement 12).

 

New Microbial Pathways

acetone degradation (to methylglyoxal)

aminopropanol biosynthesis

aminopropanol phosphate biosynthesis

benzene degradation

catechol degradation to 2-oxopent-4-enoate II

methylglyoxal degradation III

methylglyoxal degradation IV

methylglyoxal degradation V

methylglyoxal degradation VII

methylglyoxal degradation VIII

m-xylene degradation to m-toluate

naphthalene degradation

phenol degradation I (aerobic)

p-xylene degradation to p-toluate

threonine degradation I

threonine degradation IV

New Microbial Pathways from EcoCyc

degradation of purine deoxyribonucleosides

degradation of purine ribonucleosides

degradation of pyrimidine deoxyribonucleosides

degradation of pyrimidine ribonucleosides

A New Microbial Pathway from ScoCyc

actinorhodin biosynthesis

Updated Microbial Pathways

acrylonitrile degradation

alanine degradation II

alanine degradation III

alanine degradation IV

β-alanine biosynthesis III

D-lactate fermentation to propionate and acetate

Entner-Doudoroff pathway III (semi-phosphorylative)

galactonate degradation

galactose degradation I

GDP-D-rhamnose biosynthesis

glucose degradation (oxidative)

glycolysis I

4-hydroxyphenylacetate degradation

methylglyoxal degradation II

phenylmercury acetate degradation

superpathway of methylglyoxal degradation in E. coli

superpathway of threonine metabolism

threonine degradation II

threonine degradation III (to methylglyoxal)

toluene degradation to benzoate

New Plant Pathways

13-LOX and 13-HPL pathway

9-LOX and 9-AOS pathway

9-LOX and 9-HPL pathway

abietic acid biosynthesis

amaranthin biosynthesis

betacyanin biosynthesis

betacyanin biosynthesis (via dopamine)

betalain biosynthesis (to betalamic acid)

betanidin degradation

betaxanthin biosynthesis

betaxanthin biosynthesis (via dopamine)

betaxanthin biosynthesis (via dopaxanthin)

crocetin biosynthesis

crocetin esters biosynthesis

dehydroabietic acid biosynthesis

divinyl ether biosynthesis I (9-LOX)

divinyl ether biosynthesis II (13-LOX)

DMNT biosynthesis

isopimaric acid biosynthesis

levopimaric acid biosynthesis

neoabietic acid biosynthesis

oleoresin monoterpene volatiles biosynthesis

oleoresin sesquiterpene volatiles biosynthesis

palustric acid biosynthesis

S-methylmethionine cycle

Updated Plant Pathways

glycolysis IV

homomethionine biosynthesis

jasmonic acid biosynthesis

phospholipid biosynthesis II

starch degradation

sucrose degradation III

New Superpathways

superpathway of betalain biosynthesis

superpathway of cytosolic glycolysis (plants), pyruvate dehydrogenase and TCA cycle

superpathway of diterpene resin acids biosynthesis

superpathway of lipoxygenase

superpathway of methionine biosynthesis (by sulfhydrylation)

superpathway of methionine degradation

superpathway of oleoresin turpentine biosynthesis

superpathway of sulfide oxidation (Acidithiobacillus ferrooxidans)

superpathway of sulfur metabolism (Desulfocapsa sulfoexigens)

superpathway of sulfur oxidation (Acidianus ambivalens)

superpathway of thiosulfate metabolism (Desulfovibrio sulfodismutans)

---

Release Notes for MetaCyc Version 10.6

Released on January 10, 2007

MetaCyc KB Statistics

Pathways	879
Reactions	6113
Enzymes	3841
Chemical Compounds	5978
Organisms	902
Citations	11934

New and Updated Pathways

93 new pathways were added to MetaCyc since the last release. In addition, we significantly revised 32 pathways, by adding commentary and updated enzyme and gene information, for a total of 125 updated pathways.

In microbial metabolism we added 37 new pathways, and significantly enhanced 27 pathways, for a total of 64 pathways.

We expanded our coverage of lysine degradation by adding five new pathways from bacteria, yeasts, fungi and mammals. We also added a new superpathway that provides an overview of the many different initial reactions in lysine degradation. Additional degradation topics covered in this release include new and modified pathways for the degradation of phenylalanine, ornithine, nitroethane, orthanilate, sucrose, carbon tetrachloride, 2-nitropropane and carbon disulfide. New and modified biosynthetic pathways include homocysteine, siroheme amide, dolichyldiphosphooligosaccharide and phenylalanine. Other pathways include new variants for hydrogen oxidation and the reductive TCA cycle, an improved Calvin cycle, and an expanded methanogenesis from carbon dioxide pathway.

We significantly expanded our coverage of microbial sulfur metabolism, adding and modifying pathways for the oxidation, reduction and disproportionation of sulfur compounds, including the inorganic compounds sulfide, elemental sulfur, thiosulfate, tetrathionate, sulfite and sulfate, as well as organosulfur compounds such as homocysteine, methionine, sulfoacetaldehyde and benzenesulfonate.

In plant metabolism we added 52 new pathways, and enhanced 5 pathways, for a total of 57 pathways.

Eight new plant alkaloid biosynthesis pathways have been added to this release, improving the comprehensiveness of well-characterized alkaloid pathways in the MetaCyc collection. In addition, nine biosynthetic pathways of unusual fatty acids found in certain plant seed oils have been reviewed. Several metabolic pathways of carbohydrates (e.g. the raffinose series , including stachyose, ajugose, etc), carotenoid and anthocyanin pigments (e.g. astaxanthin, bixin, shisonin, gentiodelphin and anthocyanidin) and flavonols (e.g. the pharmaceutically important syringetin or the food aroma compound raspberry ketone) have been introduced. Finally, we added a pathway for the biosynthesis of the molybdenum cofactor (moco), which binds the transition element molybdenum.

We have also updated pathways in the areas of flavonoid, phytoalexins and lipid biosynthesis.

In animal metabolism we imported 3 new pathways from HumanCyc, and curated one new pathway, for a total of 4 pathways.

Our coverage of cholesterol biosynthesis was expanded by adding two new pathways and a superpathway from HumanCyc.  The new pathways show other biosynthetic intermediates that can occur, and the superpathway provides an overview of these routes. Another new pathway describes the degradation of L-cysteine in mammals.

Special thanks: We would like to thank Dr. Ruth Welti for her help in updating the glycolipid and phospholipid desaturation pathways.

New Microbial Pathways

carbon disulfide oxidation II (aerobic)

carbon tetrachloride degradation I

carbon tetrachloride degradation II

carbon tetrachloride degradation III

homocysteine biosynthesis

hydrogen oxidation II (aerobic)

lysine degradation IV

lysine degradation V

lysine degradation VI

lysine degradation VII

lysine degradation VIII

lysine degradation IX

nitroethane degradation

reductive TCA cycle II

siroheme amide biosynthesis

sucrose degradation IV

sulfate activation for sulfonation

sulfide oxidation II (sulfide dehydrogenase)

sulfide oxidation IV (sulfur dioxygenase)

sulfite oxidation I (sulfite oxidoreductase)

sulfite oxidation II

sulfite oxidation III

sulfite oxidation IV

sulfur disproportionation II (aerobic)

sulfur reduction I

sulfur reduction II (via polysulfide)

tetrathionate oxidation

tetrathionate reduction I (to thiosulfate)

tetrathionate reductiuon II (to trithionate)

thiosulfate disproportionation I (thiol-dependent)

thiosulfate disproportionation II (non thiol-dependent)

thiosulfate disproportionation III (rhodanese)

thiosulfate oxidation II (multienzyme complex)

thiosulfate oxidation III (via tetrathionate)

New Animal Pathways

cholesterol biosynthesis II (via 24,25-dihydrolanosterol)

cholesterol biosynthesis III (via desmosterol)

L-cysteine degradation III

Updated Microbial Pathways

benzenesulfonate degradation

Calvin cycle

carbon disulfide oxidation I (anaerobic)

dolichyldiphosphooligosaccharide biosynthesis

homocysteine degradation

hydrogen oxidation I (aerobic)

interconversion of arginine, ornithine and proline (Stickland reaction)

L-cysteine degradation I

lysine degradation I

methanogenesis from CO₂

methionine degradation I (to homocysteine)

2-nitropropane degradation

ornithine degradation (proline biosynthesis)

orthanilate degradation

phenylalanine biosynthesis I

phenylalanine degradation II

sucrose degradation I

sulfate reduction I (assimilatory)

ulfate reduction II (assimilatory)

sulfate reduction III (dissimilatory)

sulfate reduction IV (dissimilatory)

sulfide oxidation I (sulfide-quinone reductase)

sulfoacetaldehyde degradation

sulfur disproportionation I (anaerobic)

sulfur oxidation I (aerobic)

sulfur oxidation II (Fe⁺³-dependent)

thiosulfate oxidation I (to tetrathionate)

New Plant Pathways

abscisic acid glucose ester biosynthesis

ajmaline and sarpagine biosynthesis

ajugose biosynthesis I (galactinol-dependent)

ajugose biosynthesis II (galactinol-independent)

α-amyrin biosynthesis

α-eleostearic acid biosynthesis

anthocyanidin sophoroside metabolism

arachidonate and eicosapentaenoate biosynthesis

astaxanthin biosynthesis

bixin biosynthesis

calendic acid biosynthesis

calystegine biosynthesis

canthaxanthin biosynthesis

chalcone 2'-O-glucoside biosynthesis

chrysin biosynthesis

chrysophanol biosynthesis

coumarin metabolism (to melilotic acid)

Δ5-eicosenoate biosynthesis

A series fagopyritols biosynthesis

B series fagopyritols biosynthesis

Δ6-hexadecenoate biosynthesis

dimorphecolate biosynthesis

esculetin biosynthesis

galactosylcyclitol biosynthesis

gentiodelphin biosynthesis

hyoscyamine and scopolamine biosynthesis

kaempferol glucoside biosynthesis (Arabidopsis)

kaempferol triglucoside biosynthesis

linear furanocoumarin biosynthesis

methylthiopropionate biosynthesis

molybdenum cofactor biosynthesis

N-glucosylnicotinate metabolism

nicotine biosynthesis

N-methyl-Δ¹-pyrrolinium cation biosynthesis

palmitoleate biosynthesis

petroselinate biosynthesis

phaseic acid biosynthesis

punicic acid biosynthesis

pyridine nucleotide cycling (plants)

quercetin glucoside biosynthesis (Arabidopsis)

raspberry ketone biosynthesis

rutin biosynthesis

sanguinarine and macarpine biosynthesis

secologanin and strictosidine biosynthesis

shisonin biosynthesis

stachyose biosynthesis

syringetin biosynthesis

ternatin C5 biosynthesis

vindoline and vinblastine biosynthesis

Updated Plant Pathways

aurone biosynthesis

camalexin biosynthesis

flavonol biosynthesis

glycolipid desaturation pathway

phospholipid desaturation pathway

New Superpathways

superpathway of anthocyanin biosynthesis (from delphinidin-3-O-glucoside)

superpathway of anthocyanin biosynthesis (from pelargonidin-3-O-glucoside)

superpathway of anthocyanin biosynthesis (from cyanidin and cyanidin-3-O-glucoside)

superpathway of cholesterol biosynthesis

superpathway of lysine degradation

superpathway of sulfide oxidation (Starkeya novella)

---

Release Notes for MetaCyc Version 10.5

Released on September 8, 2006

MetaCyc KB Statistics

Pathways	800
Reactions	5871
Enzymes	3527
Chemical Compounds	5253
Organisms	729
Citations	10658

 

New and Updated Pathways

44 new pathways were added to MetaCyc since the last release. In addition, we significantly revised 24 pathways, by adding commentary and updated enzyme and gene information, for a total of 68 updated pathways.

In microbial metabolism we added 30 new pathways, and significantly enhanced 17 pathways, for a total of 47 pathways.

New pathways include the biosynthesis of cell components such as tetrapyrroles, lipids and peptidoglycan, and the degradation of several aromatic compounds, including cyanurate, melamine, N-cyclopropylmelamine, and 4-toluenesulfonate.

We significantly expanded our coverage of methanogenesis, adding pathways for the biosynthesis of several methanogenic cofactors including coenzyme B, coenzyme M, factor 420, factor 430, and methanofuran, a pathway for the regeneration of coenzyme B and coenzyme M from their heterosulfide, seven new pathways for methanogenesis from different substrates, and a lactate biosynthetic pathway from the methanogen Methanocaldococcus jannaschii, in which lactate is used as a precursor for factor 420.

We also added two new superpathways for aerobic toluene degradation and the degradation of pentoses and pentitols, and imported 4 new pathways from EcoCyc, covering lipoate biosynthesis and incorporation, lipopolysaccharide biosynthesis, and the degradation of ethylene glycol.

In addition to creating new pathways, we updated pre-existing pathways in the following areas: heme biosynthesis; lipoate biosynthesis; NAD biosynthesis; pentitol degradation; benzoyl-CoA degradation; other aromatic compounds degradation; and lysine degradation and fermentation.

Finally, we reorganized some of our existing pathways, breaking them into several shorter conserved pathways which are linked to each other. Doing so decreases redundancy in MetaCyc, and will improve future pathway predictions by our PathoLogic software. Reorganized pathways include biosynthesis of tetrapyrrole-derived molecules, including heme, chlorophyll and cobalamine, and degradative pathways of aromatic compounds that proceed through the intermediates 2-oxopent-4-enoate and glutaryl-CoA.

In plant metabolism we added 12 new pathways, and enhanced 7 pathways, for a total of 19 updated pathways.

A variety of new plant pathways have been added to the database. They include acetyl-CoA biosynthesis, mitochondrial membrane lipid cardiolipin biosynthesis, activation of the secondary metabolite glucosinolate, and biosynthesis of the medicinal alkaloid morphine. Biosynthetic pathways of the phenylpropenoids ferulate, sinapate and coumarin have also been added. The former two compounds are precursors to UV-protecting hydroxycinnamyl esters in plants, whereas coumarins are recognized for their pharmacological and therapeutic properties in humans. Other new additions include the biosynthetic pathways of the important terpenoids artemisinin (the most potent anti-malaria drug) and soybean saponin, as well as salvianin, a major anthocyanin in the Labiatae family that contributes to flower coloration.

We have also updated a number of existing pathways including abscisic acid and carotenoid biosyntheses, and several glucosinolate biosynthesis pathways.

In animal metabolism we imported 2 new pathways from HumanCyc, covering the degradation of anandamide, a member of the endocannabinoid class of signaling lipids, and of dopamine, a neurotransmitter and physiological regulator.

We would like to express our gratitude to Drs. Maor Bar-Peled, Ed Cahoon, Clint Chapple, Peter Facchini, Jonathan Page and David Seigler for their invaluable contribution to the identification and curation of many of the plant pathways in the last two MetaCyc releases.  We would also like to thank Dr. Rob Gunsalus for his suggestions concerning methanogenesis.

New Microbial Pathways

coenzyme B/coenzyme M regeneration

cyanurate degradation

ethylene glycol degradation (from EcoCyc)

factor 420 biosynthesis

factor 420 polyglutamylation

factor 430 biosynthesis

glutaryl-CoA degradation

KDO₂-lipid A biosynthesis I (from EcoCyc)

lactate biosynthesis

Lipid A-core biosynthesis (from EcoCyc)

lipoate biosynthesis and incorporation II (from EcoCyc)

melamine degradation

methanofuran biosynthesis

methanogenesis from dimethylamine

methanogenesis from dimethylsulfide

methanogenesis from methanethiol

methanogenesis from methylamine

methanogenesis from methylthiopropionate

methanogenesis from tetramethylammonium

methanogenesis from trimethylamine

methyl-coenzyme M oxidation to CO₂

N-cyclopropylmelamine degradation

2-oxopent-4-enoate degradation

peptidoglycan biosynthesis II

siroheme biosynthesis

super pathway of aerobic toluene degradation

superpathway of pentose and pentitol degradation

tetrapyrrole biosynthesis I

tetrapyrrole biosynthesis II

4-toluenesulfonate degradation II

New Animal Pathways

anandamide degradation (from HumanCyc)

dopamine degradation (from HumanCyc)

Updated Microbial Pathways

benzoyl-CoA degradation II (anaerobic)

benzoate degradation I (aerobic)

benzoyl-CoA degradation III (anaerobic)

D-arabitol degradation

heme biosynthesis I

heme biosynthesis II

lipoate biosynthesis and incorporation I

lysine degradation II

lysine fermentation to acetate and butyrate

methanogenesis from acetate

methanogenesis from methanol

NAD biosynthesis III

pentachlorophenol degradation

peptidoglycan biosynthesis I

pyruvate dehydrogenase complex pathway

ribitol degradation

xylitol degradation

New Pant Pathways

acetyl-CoA biosynthesis (from citrate)

artemisinin biosynthesis

capsanthin and capsorubin biosynthesis

cardiolipin biosynthesis

coumarin biosynthesis (via 2-coumarate)

ferulate and sinapate biosynthesis

glucosinolate breakdown

lactucaxanthin biosynthesis

morphine biosynthesis

salvianin biosynthesis

soybean saponin biosynthesis (via soyasapogenol B)

superpathway of acetyl-CoA biosynthesis

Updated Plant Pathways

abscisic acid biosynthesis

carotenoid biosynthesis

glucosinolate biosynthesis from homomethionine

glucosinolate biosynthesis from phenylalanine

glucosinolate biosynthesis from tryptophan

phospholipase pathway

triacylglycerol biosynthesis

---

Release Notes for MetaCyc Version 10.1

Released on May 19, 2006.

MetaCyc KB Statistics

Pathways	759
Reactions	5797
Enzymes	3370
Chemical Compounds	5095
Organisms	686
Citations	9799

New and Updated Pathways

47 new pathways were added to MetaCyc since the last release. In addition, we significantly revised 21 pathways, by adding commentary and updated enzyme and gene information, for a total of 68 updated pathways.

In microbial/animal metabolism we added 11 new pathways, and significantly enhanced 13 pathways, for a total of 24 pathways.

In central metabolism we have updated several pathways covering variants of the tricarboxylic acid (TCA) cycle (both complete and incomplete cycles), glycolysis, and pyruvate fermentation. We updated our coverage of amino-acid biosynthesis and degradation pathways with new pathways for the biosynthesis of isoleucine, arginine, and β-alanine, and for the degradation of tyrosine, phenylalanine and hydroxyproline. We also added a new variant of 2-oxobutanoate degradation, and a new pathway for 2-methylbutyrate biosynthesis.

In plant metabolism we added 36 new pathways, and enhanced 8 pathways, for a total of 44 pathways.

New plant primary metabolism pathways include several pathways of fatty acid and sugar-nucleotide metabolism.

New plant secondary metabolism pathways include the biosynthesis of several anthocyanins and the degradation of chlorophyll. In addition, we added four new pathways describing the biosynthesis of geranyl diphosphate, geranylgeranyl diphosphate and trans,trans-farnesyl diphosphate, which simplify the metabolism of terpenoids. Moreover, four important biosynthetic pathways of Cannabis and hops (the latter being involved in the flavouring of beer) have been added to the database.

We have also updated and revised several existing pathways: ascorbate biosynthesis; aurone biosynthesis; coenzyme A biosynthesis; isoflavonoid biosynthesis II; NAD/NADH phosphorylation and dephosphorylation; sulfate assimilation III; triacylglycerol degradation; and wighteone and luteone biosynthesis.

Update of EC Reactions

During this quarter we have updated the reactions in MetaCyc with the latest information (as of February 2006) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by  incorporating supplement 11 (see Enzyme Nomenclature Supplement 11).

New Microbial/Animal Pathways

arginine biosynthesis III

β-alanine biosynthesis IV

biotin-carboxyl carrier protein

4-hydroxyproline degradation II

isoleucine biosynthesis II

isoleucine biosynthesis III

isoleucine biosynthesis IV

isoleucine biosynthesis V

2-methylbutyrate biosynthesis

2-oxobutanoate degradation I

tyrosine degradation II

Updated Microbial/Animal Pathways

acetyl-coa fermentation to butyrate

CMP-KDO biosynthesis I

fatty acids biosynthesis (initial steps)

glycolysis III

4-hydroxyproline degradation I

incomplete reductive TCA cycle

isoleucine biosynthesis I

2-oxobutanoate degradation I

phenylalanine degradation I

pyruvate fermentation to acetate and alanine

pyruvate fermentation to acetate and lactate

TCA cycle variation I

tyrosine degradation I

New Plant Pathways

acacetin biosynthesis

acyl-ACP desaturation pathway

acyl-ACP thioesterase pathway

acyl-CoA synthetase pathway

acyl-CoA thioesterase pathway

anthocyanin biosynthesis (delphinidin 3-O-glucoside)

anthocyanin biosynthesis (pelargonidin 3-O-glucoside, cyanidin 3-O-glucoside)

bitter acids biosynthesis

cannabinoid biosynthesis

chlorophyll a degradation

CMP-KDO biosynthesis II (from D-arabinose 5-phosphate)

cohumulone biosynthesis

6'-deoxychalcone metabolism

fatty acid β-oxidation II (plant, saturated)

fatty acid β-oxidation III (plant, unsaturated, odd number)

fatty acid β-oxidation IV (plant, unsaturated, even number)

GDP-L-galactose biosynthesis

geranyldiphosphate biosynthesis

geranylgeranyldiphosphate biosynthesis I (cytosolic)

geranylgeranyldiphosphate biosynthesis II (plastidic)

hesperitin glycoside biosynthesis

humulone biosynthesis

leucodelphinidin biosynthesis

lysine biosynthesis VI

naringenin glycoside biosynthesis

pelargonidin conjugates biosynthesis

phytol salvage pathway

ponciretin biosynthesis

rose anthocyanin biosynthesis

sakuranetin biosynthesis

sphingolipid biosynthesis (plants)

superpathway of fatty acid biosynthesis II (plant)

trans,trans-farnesyl diphosphate biosynthesis

trigonelline biosynthesis

UDP-D-apiose biosynthesis (from UDP-D-glucuronate)

xanthohumol biosynthesis

Updated Plant Pathways:

ascorbate biosynthesis

aurone biosynthesis

coenzyme A biosynthesis

isoflavonoid biosynthesis II

NAD/NADH phosphorylation and dephosphorylation

sulfate assimilation III

triacylglycerol degradation

wighteone and luteone biosynthesis

---

Release Notes for MetaCyc Version 10.0

Released on March 13, 2006.

MetaCyc KB Statistics

Pathways	719
Reactions	5598
Enzymes	3165
Chemical Compounds	4907
Organisms	638
Citations	9149

New and Updated Pathways

47 new pathways were added to MetaCyc since the last release. In addition, we significantly revised 15 pathways, by adding commentary and updated enzyme and gene information, for a total of 62 updated pathways.

In microbial/animal metabolism we added 19 new pathways, and significantly enhanced 9 pathways, for a total of 28 pathways.

Among the topics that received special attention this quarter were amino acid degradation pathways, including the branched chain amino acids (leucine, isoleucine, and valine), glutamate, methionine, tryptophan, and phenylalanine. Two new degradation pathways of the aromatic pyridine ring were added: nicotinate degradation II, which is an aerobic pathway, and nicotinate degradation III, which is an anaerobic fermentation pathway. Nicotinate (also known as niacin, or vitamin B₃) is important in both biological and industrial processes. Additionally, a superpathway of nicotinate degradation was created that includes all three pathway variants of nicotinate degradation.

In plant metabolism we added 28 new pathways, and enhanced 6 pathways, for a total of 34 pathways.

New plant primary metabolism pathways include biosynthesis of the the purine precursors of caffeine and theobromine, very long chain fatty acids, sorbitol, chlorophyll, gibberellin and its precursors, and phytyl-PP. A pathway involved in NAD/NADH phosphorylation and dephosphorylation was also added.

New plant secondary metabolism pathways include the biosynthesis of an isoflavonoid (6,7,4'-trihydroxyisoflavone), a flavone (luteolin), a flavonol (pinobanskin), a stilbene (pinosylvin) and a cinnamic acid derivative (rosmarinic acid). In addition, four new pathways describe the biosynthesis of the purine alkaloids caffeine and theobromine.

We have also updated and revised several existing pathways, including ureide degradation, resveratrol biosynthesis, biotin biosynthesis, sorbitol utilization, gibberellin inactivation, and chlorophyllide a biosynthesis.

New microbial/animal pathways:

1,6-anhydro-N-acetylmuramic acid recycling

2-keto glutarate dehydrogenase complex

ADP-L-glycero-β-D-manno-heptose biosynthesis

branched-chain α-keto acid dehydrogenase complexes

gibberellin biosynthesis IV (Gibberella fujikuroi)

glutamate degradation VI (to pyruvate)

glutamate degradation VIII (to propionate)

glycogen biosynthesis II (from UDP-D-Glucose)

isoleucine degradation II

leucine degradation II

leucine degradation III

methionine degradation III

mevalonate degradation

nicotinate degradation II

nicotinate degradation III

phenylalanine degradation III

superpathway of nicotinate degradation

tryptophan degradation VIII (to tryptophol)

valine degradation II

Updated microbial/animal pathways:

glutamate degradation I

glutamate degradation II

glutamate degradation VII

glycolysis II

isoleucine degradation I

leucine degradation I

pyruvate dehydrogenase complex

reductive tricarboxylic acid cycle

valine degradation I

New plant pathways:

6,7,4'-trihydroxyisoflavone biosynthesis

caffeine biosynthesis I

caffeine biosynthesis II (via paraxanthine)

chlorophyll a biosynthesis I

chlorophyll a biosynthesis II

chlorophyll cycle

ent-kaurene biosynthesis

GA₁₂ biosynthesis

gibberellin biosynthesis I (non C-3, non C-13 hydroxylation)

gibberellin biosynthesis II (early C-3 hydroxylation)

gibberellin biosynthesis III (early C-13 hydroxylation)

luteolin biosynthesis

NAD/NADH phosphorylation and dephosphorylation

phytyl-PP biosynthesis

pinobanksin biosynthesis

pinosylvin metabolism

purine degradation

rosmarinic acid biosynthesis I

rosmarinic acid biosynthesis II

salvage pathways of purine nucleosides II (plant)

SAM cycle

sorbitol biosynthesis

superpathway of GA₁₂ biosynthesis

superpathway of gibberellin biosynthesis

superpathway of rosmarinic acid biosynthesis

theobromine biosynthesis I

theobromine biosynthesis II (via xanthine)

very long chain fatty acid biosynthesis

Updated plant pathways:

biotin biosynthesis II

chlorophyllide a biosynthesis

gibberellin inactivation

resveratrol biosynthesis

sorbitol utilization

ureide degradation

---

Release Notes for MetaCyc Version 9.6

Released on December 15, 2005.

MetaCyc KB Statistics

Pathways	692
Reactions	5520
Enzymes	3029
Chemical Compounds	4817
Organisms	601
Citations	8599

New and Updated Pathways

81 new pathways were added to MetaCyc since the last release. In addition, we significantly revised 36 pathways, by adding commentary and updated enzyme and gene information, for a total of 117 updated pathways.

In microbial/animal metabolism we added 29 new pathways, and significantly enhanced 33 pathways, for a total of 62 pathways.

Topics that received special attention this quarter include nitrogen metabolism (citrulline, arginine, 4-aminobutyrate, urea, and polyamines), arsenic detoxification, and bacterial degradation of both naturally occurring compounds and xenobiotics. We expanded our coverage of thiol metabolism to include glutathione amide, glutathionylspermidine and trypanothione, and continued to enhance our coverage of amino acid metabolism with various pathways of arginine, cysteine, histidine, glutamate, and proline metabolism.

In plant metabolism we added 52 new pathways, and enhanced 3 pathways, for a total of 55 pathways.

New plant primary metabolism pathways include plant variants of amino acid metabolism (glutamate, methionine, and proline), and pathways of fatty acid and UDP-sugar metabolism.

New microbial/animal pathways:

4-aminobutyrate degradation II

arginine degradation IX (D-arginine dehydrogenase pathway)

arginine degradation XI

arsenate detoxification I

arsenate detoxification II

arsenate reduction (respiratory)

arsenite oxidation (respiratory)

biotin biosynthesis III

citrulline-nitric oxide cycle

creatinine degradation II

creatinine degradation III

glutathione amide metabolism

glutathionylspermidine biosynthesis

histidine degradation II

histidine degradation III

histidine degradation V

IAA biosynthesis IV

IAA biosynthesis V

imidazole-lactate degradation

proline biosynthesis V (from arginine)

protein citrullination

putrescine biosynthesis I

putrescine biosynthesis II

putrescine biosynthesis III

putrescine degradation III

putrescine degradation IV

putrescine degradation V

superpathway of citrulline metabolism

urea cycle

Updated microbial/animal pathways:

3-phenylpropionate degradation

4-aminobutyrate degradation I

4-hydroxymandelate degradation

aerobactin biosynthesis

arginine degradation I

arginine degradation II

arginine degradation III

arginine degradation IV

arginine degradation V

biotin biosynthesis I

citrulline degradation

creatinine degradation I

cysteine biosynthesis II

gallate degradation I

gallate degradation II

glutamate degradation I

glutamate degradation II

heme biosynthesis II

methylgallate degradation

nicotinate degradation

nopaline degradation

octopine degradation

proline degradation I

putrescine degradation I

putrescine degradation II

quinate degradation

shikimate degradation

spermidine biosynthesis

spermine biosynthesis

toluene degradation II

toluene degradation III

toluene degradation V

trypanothione biosynthesis

New plant pathways:

6-methoxymellein biosynthesis

aerobic respiration -- electron donor III

aloesone biosynthesis

benzoxazinoid glucosides biosynthesis

β-pyrazole-1-ylalanine biosynthesis

canavanine biosynthesis

canavanine degradation

coniferin metabolism

curcumin glucoside biosynthesis

cyclopropane and cyclopropene fatty acid biosynthesis

DIBOA / DIMBOA biosynthesis

DIMBOA-Glc degradation

fatty acid biosynthesis - initial steps II

GDP-L-fucose biosynthesis I (from GDP-D-mannose)

GDP-L-fucose biosynthesis II (from L-fucose)

gibberellin inactivation pathway I

gibberellin inactivation pathway II (early-13-hydroxylation GAs)

glutamate biosynthesis V

glutamate degradation X

glycerol degradation IV

inositol oxidation pathway

kievitone biosynthesis

lathyrine biosynthesis

lipid-dependent phytate biosynthesis I (via Ins(1,4,5)P₃)

lipid-dependent phytate biosynthesis II (via Ins(1,3,4)P₃)

lipid-independent phytate biosynthesis

lupeol biosynthesis

methionine salvage pathway II

mimosine biosynthesis

monolignol glucosides biosynthesis

pentaketide chromone biosynthesis

phylloquinone biosynthesis

phytate degradation I

phytate degradation II

proline biosynthesis IV

proline degradation III

resveratrol biosynthesis

sorbitol degradation II

superpathway of isoflavonoids (via naringenin)

superpathway of pterocarpan biosynthesis (via daidzein)

superpathway of pterocarpan biosynthesis (via formononetin)

tetrahydroxyxanthone biosynthesis (from 3-hydroxybenzoate)

tetrahydroxyxanthone biosynthesis (from benzoate)

UDP-D-galacturonate biosynthesis I (from UDP-D-glucuronate)

UDP-D-galacturonate biosynthesis II (from D-galacturonate)

UDP-D-xylose biosynthesis

UDP-L-arabinose biosynthesis I (from UDP-xylose)

UDP-L-arabinose biosynthesis II (from L-arabinose)

volatile benzenoid ester biosynthesis

volatile cinnamoic ester biosynthesis

wighteone and luteone biosynthesis

willardiine and isowillardiine biosynthesis

Updated plant pathways

asparagine biosynthesis II

gibberellin biosynthesis

sinapate ester biosynthesis

---

Release Notes for MetaCyc Version 9.5

Released on September 30, 2005.

MetaCyc KB Statistics

Pathways	621
Reactions	5428
Enzymes	2698
Chemical Compounds	4620
Organisms	506
Citations	7369

 

New and Updated Pathways

During this quarter we have added 30 new pathways to MetaCyc, and updated the information in 15 additional pathways, for a total of 45 new or modified pathways .

In microbial metabolism, we focused primarily on the biochemistry of the important thiols glutathione and mycothiol, the transformations of choline, γ-butyrobetaine, glycine betaine and carnitine, and the biosynthesis and degradation of the amino acids methionine and cysteine. In addition, we added pathways covering the degradation of butanediol and the biosynthesis of the enzyme cofactor lipoate. We also rewrote the pathway for the biosynthesis of teichoic acid, an important component of the cell wall of Gram-positive bacteria.

In plant metabolism , we have added many new pathways involved in the primary metabolism of plants. Main topics were carbohydrate (galactose, mannitol, and sucrose) metabolism, membrane phospholipids (choline I and II) biosynthesis, enzyme cofactors (tetrahydrofolate, formyltetrahydrofolate and biotin) biosynthesis, asparagine degradation, and biosynthesis of the abiotic stress response secondary metabolite, β-alanine betaine. We also added  two biosynthetic pathways of plant alkaloids (berberine and (S)-reticuline), and covered the biosynthesis of β-alanine and pantothenate.

Update of EC Reactions

During this quarter we have updated the reactions in MetaCyc with the latest information (as of January 2005) from the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB), by  incorporating supplement 10 (see Enzyme Nomenclature Supplement 10).

New Cellular Location Ontology

We have introduced an improved and expanded cellular component ontology that is used both for specifying enzyme cellular locations, and for describing the compartments involved in transport reactions. Our vocabulary of cellular component terms was expanded from 35 to over 150 terms, which are now organized into classes, subclasses and instances. The terms are also related to each other using multiple relationships such as 'component-of' and 'surrounded-by'. For example, the term "inner membrane (sensu Gram-negative bacteria)" is surrounded by the terms "periplasmic space (sensu Gram-negative bacteria)" and "cell wall (sensu Gram-negative bacteria)", and surrounds the terms "cytoplasm" and "cytosol". These new relationships between cellular locations will allow us to introduce more robust querying, and a better graphical display of protein locations. Whenever possible, the new ontology terms have a cross-reference to the Gene Ontology Consortium's (GO) cellular component ontology.

More Chemical Structures

We also continued the addition of chemical structures to our compound library. We have added 724 new structures during this period, and now have 4316 compounds with structures.

Pathway Tools Software Enhancements

There have been many enhancements to the Pathway Tools software which is used to query MetaCyc. Please see the Pathway Tools Release Notes for more details.

New microbial pathways:

carnitine degradation II

carnitine degradation III

choline degradation II

γ-butyrobetaine degradation

γ-glutamyl cycle

glutathione redox reactions I

glutathione-mediated detoxification

glycine betaine biosynthesis II (Gram-positive bacteria)

glycine betaine degradation

putrescine degradation II (from EcoCyc)

Updated microbial pathways:

butanediol biosynthesis

choline degradation I

formaldehyde oxidation III (mycothiol-dependent)

glycine betaine biosynthesis I (Gram-negative bacteria)

glycine betaine biosynthesis IV (from glycine)

glutathione redox reactions II

L-cysteine degradation I

lipoate biosynthesis and incorporation  (from EcoCyc)

methionine biosynthesis III

methionine biosynthesis IV

methionine degradation I

mycothiol biosynthesis

mycothiol-mediated detoxification

mycothiol oxidation

teichoic acid (poly-glycerol) biosynthesis

New plant pathways

aerobic respiration

asparagine degradation II

asparagine degradation III

β-alanine betaine biosynthesis

β-alanine biosynthesis I

β-alanine biosynthesis II

β-alanine biosynthesis III

berberine biosynthesis

biotin biosynthesis III

choline biosynthesis II

choline biosynthesis III

formylTHF biosynthesis I

galactose degradation III

mannitol biosynthesis

mannitol degradation II

pantothenate biosynthesis II

pantothenate biosynthesis III

(S)-reticuline biosynthesis

sucrose degradation to ethanol and lactate (anaerobic)

tetrahydrofolate biosynthesis I

---

Release Notes for MetaCyc Version 9.1

Released on May 23, 2005.

MetaCyc KB Statistics

Pathways	601
Reactions	5273
Enzymes	2458
Chemical Compounds	4496
Organisms	456
Citations	6566

 

This last quarter has been very productive at MetaCyc. We have added a total of 62 new pathways, and updated the information in 20 additional pathways!

In microbial metabolism, we added 20 new pathways. These pathways include expanded coverage of the metabolism of the amino acids lysine, isoleucine and tryptophan, the biosynthesis of the important redox cofactor nicotinamide adenine dinucleotide (NAD), a superpathway that ties together the different pathways for aerobic degradation of aromatic compounds found in Pseudomonas, the metabolism of the sugar trehalose, and a few new pathways for the degradation of xenobiotic compounds.

aromatic compound degradation (aerobic)

benzoate degradation I (aerobic)

indole-3-acetate degradation to anthranilate

isethionate degradation

lysine biosynthesis II

lysine biosynthesis III

lysine biosynthesis V

NAD biosynthesis II (from tryptophan)

NAD salvage pathway I

superpathway of isoleucine biosynthesis

superpathway of NAD biosynthesis in eukaryotes

trehalose biosynthesis IV

trehalose biosynthesis V

trehalose degradation II (high osmolarity)

trehalose degradation III

trehalose degradation IV

trehalose degradation V

tryptophan degradation V (via indole-3-acetamide)

tryptophan degradation VI (side chain pathway)

tryptophan degradation VII (via tryptamine)

In plant metabolism we added 38 new pathways. New plant pathways include plant variants of amino acid metabolism, pathways of fatty acid metabolism, plant hormone biosynthesis (brassinosteroids and cytokinins), and secondary metabolism (isoflavonoids, phenylpropanoids, nitrogen-containing glucosides and terpenoids).

ammonia assimilation cycle II

biochanin A conjugates interconversion

brassinosteroid biosynthesis II

capsidiol biosynthesis

choline biosynthesis

cis-zeatin biosynthesis

cytokinins 7-N-glucoside biosynthesis

cytokinins 9-N-glucoside biosynthesis

cytokinins degradation

cytokinins-O-glucoside biosynthesis

diterpene phytoalexins precursors biosynthesis

dTDP-L-rhamnose biosynthesis II

fatty acid oxidation pathway II

fatty acid oxidation pathway III

flavonol biosynthesis

formononetin conjugates interconversion

glucosinolate biosynthesis from phenylalanine

glutamate degradation IX

glyceollin biosynthesis I

glyceollin biosynthesis II

linamarin biosynthesis

linamarin degradation

maackiain biosynthesis

maackiain conjugates interconversion

medicarpin biosynthesis

medicarpin conjugates interconversion

menthol biosynthesis

phaseollin biosynthesis

phenylalanine biosynthesis III

pisatin biosynthesis

plant monoterpene biosynthesis

proline biosynthesis III

sesquiterpenoid phytoalexins biosynthesis

sinapate ester biosynthesis

sterol biosynthesis

trans-zeatin biosynthesis

tyrosine biosynthesis II

UDP-L-rhamnose biosynthesis

In mammalian metabolism we have added a cholesterol biosynthesis pathway from HumanCyc. This pathway describes the biosynthesis of cholesterol from farnesyl diphosphate in an extensive series of 22 reactions.  Combined with the existing mevalonate pathway, which is linked to it, MetaCyc now covers the complete biosynthesis of cholesterol from acetyl-CoA.

cholesterol biosynthesis

We have also incorporated the following new yeast pathways which were curated by our friends at SGD. Thank you Eurie Hong and Rama Balakrishnan!

allantoin degradation II

glutamate biosynthesis from glutamine

superpathway of NAD biosynthesis in eukaryotes

Additional yeast-specific information, provided by SGD, was added to the following existing MetaCyc pathways:

glutamate biosynthesis III

NAD biosynthesis II (from tryptophan)

NAD salvage pathway I

Besides entering new pathways, we have been working on adding commentary and updated enzyme and gene information to existing pathways. The following pathways have been revised to reflect current knowledge and to provide better commentary:

1,8-cineole degradation

anthocyanin biosynthesis

arginine biosynthesis I

arginine biosynthesis II

brassinosteroid biosynthesis I

dolichyl-diphosphooligosaccharide biosynthesis

glycine degradation II

isoflavonoid biosynthesis II

lysine biosynthesis I

lysine degradation III

NAD biosynthesis I

NAD salvage II

NAD salvage III

nylon-6 oligomer degradation

sophorosyloxydocosanoate biosynthesis

sophorosyloxydocosanoate degradation

sucrose degradation II

trehalose biosynthesis I

trehalose biosynthesis II

trehalose degradation I

In addition, we continue to expand our chemical compound library and add chemical structures to the compounds. Over 93% of our 4496 compounds have structures.

---

Release Notes for MetaCyc Version 9.0

Released on February 25, 2005.

MetaCyc KB Statistics

Pathways	547
Reactions	5046
Enzymes	2062
Chemical Compounds	3945
Organisms	341
Citations	5468

 

A total of 20 new pathways have been added to MetaCyc in this release.

In bacterial metabolism, we have expanded our coverage of ammonia oxidation and folate metabolism by adding new pathways and improving the annotation of existing ones. We have expanded our coverage of the Entner-Doudoroff pathway to include the interesting variations found in different species of archaea, added a new pathway and more information about nitro-aromatic compounds degradation, and added a pathway for the biosynthesis of myo-inositol.

In plant metabolism we continue to cover secondary metabolism, with new pathways covering the metabolism of phenylpropanoid acid, the biosynthesis of pterocarpan, and the interconversion of genistein and daidzein conjugates.

In mammalian metabolism we added four human pathways: A pathway for the biosynthesis of the catecholamine neuro transmitters (norepinephrine, epinephrine and dopamine), a pathway for the degradation of the antidepressant drug bupropion, and two pathways that cover the various routes used in the metabolism of nicotine.

We have also included three new yeast pathways, which were originally created for YeastCyc (SGD). Two of these pathways cover the biosynthesis of major constituents of the fungal plasma membrane (ergosterol and sphingolipid), and the third one describes a variant pathway for lysine biosynthesis.

The following pathways have been curated in MetaCyc since the last release:

ammonia oxidation III

ascorbate glutathione cycle

daidzein conjugates interconversion

Entner-Doudoroff pathway II (non-phosphorylative)

Entner-Doudoroff pathway III (semi-phosphorylative)

folate polyglutamylation II

folate transformations

genistein conjugates interconversion

myo-inositol biosynthesis

4-nitrobenzoate degradation

phenylpropanoid acid pathway

pterocarpan biosynthesis

The following new pathway has been imported from the EcoCyc database:

folate polyglutamylation I

 

The following new yeast pathways have been provided by the YeastCyc database, ands were curated by Eurie L. Hong. Thank you for this contribution!

ergosterol biosynthesis

lysine biosynthesis II

sphingolipid metabolism

The following new human pathways have been imported from the HumanCyc database. We thank Teresa Steininger and Tom Kilduff for curation of the catecholamine biosynthesis pathway:

bupropion degradation

catecholamine biosynthesis

nicotine degradation II

nicotine degradation III

The following existing pathways have been revised to reflect current knowledge and to provide better commentary:

ammonia oxidation I (aerobic)

ammonia oxidation II (anaerobic)

4-nitrotoluene degradation

phospholipid biosynthesis I

tetracholroethene degradation

In addition, we have continued adding chemical structures to compounds in our chemical compound library. The number of compounds with structures is now 3592.

---

Release Notes for MetaCyc Version 8.6

Released on November 8, 2004.

MetaCyc KB Statistics

Pathways	528
Reactions	4955
Enzymes	1940
Chemical Compounds	3551
Organisms	302
Citations	5050

The following new pathways have been added since the last release:

• aurone biosynthesis
• β-alanine degradation II
• formaldehyde oxidation II (GSH-dependent)
• formaldehyde oxidation IV (tetrahydrofolate pathway)
• formaldehyde oxidation V (H₄MPT pathway)
• formate oxidation to CO₂
• IAA biosynthesis II
• IAA biosynthesis III
• IAA conjugate biosynthesis I
• IAA conjugate biosynthesis II
• IAA degradation I
• IAA degradation II
• IAA degradation III
• IAA degradation IV
• isoflavonoid biosynthesis
• isoflavonoid biosynthesis, initial reactions
• methane oxidation to methanol
• methanol and methylamine oxidation to formaldehyde
• superpathway of C1 compounds oxidation to CO₂

New bacterial pathways mainly focus on C1 metabolism, specifically the different pathways employed by the methylotrophs, while new plant pathways mostly cover the different pathways employed in the metabolism of the plant hormone indole-3-acetate (IAA), and isoflavonoid biosynthesis.

Several pathways have been modified. In particular, the plant pathways for anthocyanin and flavonoid biosynthesis, and the bacterial pathways covering glycerol metabolism, formaldehyde assimilation, the degradation of β-alanine, and the degradation of lactose. Modified pathways include:

• glycerol and glycerphosphodiester degradation
• glycerol degradation II
• glycerol fermentation to 1,3-propanediol
• formaldehyde assimilation I (serine pathway)
• formaldehyde assimilation II (RuMP Cycle)
• β-alanine degradation I
• lactose degradation II
• lactose degradation III

In addition, we have added chemical structures to many of the compounds in our chemical compound library. The number of compounds with structures is now 3258.

---

Release Notes for MetaCyc Version 8.5

Released on September 17, 2004.

MetaCyc KB Statistics

Pathways	513
Reactions	4924
Enzymes	1840
Chemical Compounds	3467
Organisms	262
Citations	4662

In this upgrade we introduced stereochemistry to our compound library. While not all structures have been updated yet, we are continuously adding stereochemistry information to our library of compounds.

Another change you would notice is the labeling of genes and proteins in graphical diagrams with the initials of the organism's genus and species names. For example, the trpA gene from E. coli would now appear as Ec-trpA, and the tryptophan synthase protein will appear as tryptophan synthase (Ec). This was done to make it easier to tell genes and proteins appart, such as when genes and proteins from multiple organisms are present in a single pathway.

In addition, we are continuing our on-going curation of new and existing pathways in MetaCyc. Editing existing pathways involves adding descriptive comments, references, and enzymes, and updating the pathway to reflect the latest available information.

The following new pathways have been added since the last release:

• oxidative ethanol degradation I
• oxidative ethanol degradation II
• oxidative ethanol degradation III
• plastoquinone biosynthesis
• superpathway of taurine degradation
• formaldehyde assimilation I (serine pathway)
• formaldehyde assimilation II (RuMP cycle)

The following existing pathways were edited extensively:

• protocatechuate degradation I (meta cleavage pathway)
• D-camphor degradation
• adamantanone transformation
• galena oxidation
• taurine degradation I
• taurine degradation II
• taurine degradation III
• nitrite oxidation
• ammonia oxidation I (aerobic)
• formaldehyde oxidation I
• formaldehyde oxidation II

We also continue our effort of adding chemical structures for metabolites and other small molecules to MetaCyc. Currently 3074 of our compounds have a full molecular structure.

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Release Notes for MetaCyc Version 8.1

Released on June 23, 2004.

MetaCyc KB Statistics

Pathways	506
Reactions	4912
Enzymes	1813
Chemical Compounds	3091
Organisms	243
Citations	4455

We are continuing our on-going curation of new and existing pathways in MetaCyc. Editing existing pathways involves adding descriptive comments, references, and enzymes.

The following new pathways were curated:

• benzoyl-CoA degradation (aerobic)
• betaine biosynthesis V
• fluorene degradation II
• sulfoacetaldehyde degradation
• taurine degradation I
• taurine degradation II
• vitamin E biosynthesis

The following existing pathways were edited extensively:

• fluorene degradation I
• lignin biosynthesis
• protocatechuate degradation II (ortho-cleavage pathway)
• taurine degradation III

Many miscellaneous corrections and updates were applied. For example, the pathway for phenylalanine degradation was divided into two pathways, phenylalanine degradation II (anaerobic), which includes the reactions from phenylalanine to phenylacetate and phenylacetate degradation (anaerobic), which includes the reactions from phenylalanine to benzoyl-CoA. One enzyme in phenylacetate degradation (anaerobic) was newly curated.

In addition a new superpathway was created, β-ketoadipate pathway, which is comprised of the following two pathways: catechol degradation II (ortho-cleavage pathway) and protocatechuate degradation II (ortho-cleavage pathway).

Chemical structures for metabolites and other small molecules are being continiously added to MetaCyc. Currently 2737 of our compounds have a full molecular structure.

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Release Notes for MetaCyc Version 8.0

Released on March 12, 2004.

MetaCyc KB Statistics

Pathways	496
Reactions	4873
Enzymes	1665
Chemical Compounds	3051
Organisms	231
Citations	3771

We are continuing our on-going curation of new and existing pathways in MetaCyc. Editing existing pathways involves adding descriptive comments, references, and enzymes.

The following existing pathway was edited extensively:

• lactose and galactose degradation I

Many miscellaneous corrections and updates were applied. For example, the reactions within the superpathway of arginine degradation were reorganized into three separate subpathways:

• arginine degradation XII, which includes the reactions from arginine to putrescine
• putrescine degradation, which includes the reactions from putrescine to 4-aminobutyrate
• 4-aminobutyrate degradation, which includes the reactions from 4-aminobutyrate to succinate

Chemical structures for metabolites and other small molecules have been added to MetaCyc.

The set of enzyme inhibition categories that are represented in MetaCyc has been extended and revised. The new set includes: noncompetitive inhibitors, uncompetitive inhibitors and irreversible inhibitors, in addition to the previously existing categories of competitive inhibitors and allosteric inhibitors. A new category, inhibitors of unknown mechanism replaces two old categories that distinguished between mechanisms that were unknown because they had not been extensively curated versus ones that remained unknown after a substantial literature search, and the new category, other inhibitors, replaces a similar category in previous versions for all inhibitors that were neither competitive nor allosteric.

Categories of enzyme activation were similarly reexamined, and documentation was updated. Although no new activation categories were added, the two categories for activators whose mechanism was unknown after a minimal versus a substantial literature search were combined into a single category for activators of unknown mechanism.

See the PTools release notes for additional information on revising the enzyme inhibition and activation categories.

Enhancements to MetaCyc over the last two years are described in the article, MetaCyc: a multiorganism database of metabolic pathways and enzymes, which was recently published in the Nucleic Acids Research 2004 Database issue.

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Release Notes for MetaCyc Version 7.6

Released on November 4, 2003.

MetaCyc KB Statistics

Pathways	491
Reactions	4858
Enzymes	1618
Chemical Compounds	3029
Organisms	222
Citations	3619

The following pathways were newly curated in MetaCyc:

• carbon disulfide oxidation
• glycolysis IV
• glucosinolate biosynthesis from homomethionine
• homogalacturonan biosynthesis
• homogalacturonan degradation
• homomethionine biosynthesis
• suberin biosynthesis
• xanthophyll cycle

The following pathways were imported from EcoCyc:

• PPRP biosynthesis I
• PPRP biosynthesis II

The following pathways, which already existed in MetaCyc, were edited extensively:

• coenzyme M biosynthesis
• glucosinolate biosynthesis from tryptophan
• stachydrine degradation

Many other miscellaneous corrections and updates have been applied.

Chemical structures for metabolites and other small molecules have been added to MetaCyc.

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Release Notes for MetaCyc Version 7.5

Released on August 29, 2003.

MetaCyc KB Statistics

Pathways	492
Reactions	4831
Enzymes	1571
Chemical Compounds	2994
Organisms	214
Citations	3337

New pathways have been added to MetaCyc either from recent curation or from importing them from other Pathway/Genome Databases. Existing pathways also have been extensively edited.

The following pathways were newly curated in MetaCyc:

• ascorbate biosynthesis
• cellulose biosynthesis
• salicylic acid biosynthesis
• sulfide oxidation II

The following pathways were imported from EcoCyc:

• cyclopropane fatty acid (CFA) biosynthesis
• fructoselysine degradation
• lipoate biosynthesis and modification
• lipoate salvage and modification
• lysine degradation I

The following pathways were imported from CauloCyc:

• alanine degradation IV
• PHB biosynthesis

The following existing pathways were edited extensively in MetaCyc:

• coenzyme B biosynthesis
• thiocyanate degradation I

MetaCyc display windows now feature full lists of references in addition to links to abstracts that have been supplied previously. The list of references associated with each database object (e.g., pathway, polypeptide, etc.) is located at the bottom of the display window.

The pathway class hierarchy has been updated and improved to facilitate browsing of metabolic pathways within the BioCyc databases. The pathway hierarchy may be viewed here.

The Pathway Tools software now supports association of evidence codes with information in BioCyc databases. Evidence codes are used to indicate the type of evidence that supports assertions within these databases. For example, an evidence code can be used to describe whether a pathway was predicted computationally or elucidated experimentally. The presence of a computer icon or a flask icon, respectively, indicate computational versus experimental evidence for an assertion. Click on these icons to obtain more details about the evidence for a given entity. Evidence information will be available in subsequent MetaCyc releases. For more information see the Pathway Tools 7.5 release notes.

Many other miscellaneous corrections and updates have been applied.

Chemical structures for metabolites and other small molecules have been added to MetaCyc

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Release Notes for MetaCyc Version 7.1

Released on May 20, 2003.

MetaCyc KB Statistics

Pathways	484
Reactions	4460
Enzymes	1520
Chemical Compounds	2942
Organisms	201
Citations	3029

The following pathways were newly curated in MetaCyc:

• fructan biosynthesis
• fructan degradation
• glycolate degradation II
• glycosylglyceride desaturation pathway
• methionine biosynthesis from homoserine II
• phospholipid desaturation pathway
• starch degradation
• thiocyanate degradation II

The following existing pathways were edited extensively in MetaCyc:

• triacylglycerol biosynthesis
• TCA cycle variation IX (TCA cycle in Helicobacter pylori)

Chemical structures for 27 metabolites and other small molecules have been added to MetaCyc

Note: The pathway classification hierarchy in MetaCyc is undergoing significant revision. Please be aware that some pathways may be assigned to inappropriate locations in the hierarchy in the version 7.1 release. These assignments will be corrected in the next release.

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Release Notes for MetaCyc Version 7.0

Released on February 28, 2003.

MetaCyc KB Statistics

Pathways	477
Reactions	4429
Enzymes	1470
Chemical Compounds	2921
Organisms	190
Citations	2974

• New pathways have been added to MetaCyc either from recent curation or from importing them from other Pathway/Genome Databases. Existing pathways also have been extensively edited.

  The following pathways were newly curated in MetaCyc:

  • anaerobic ethylbenzene degradation
  • auxin biosynthesis
  • lipoxygenase pathway
  • starch biosynthesis
  • sucrose degradation III

  The following pathways were imported from EcoCyc:

  • L-ascorbate degradation
  • ethanol degradation
  • de novo biosynthesis of purine nucleotides
  • de novo biosynthesis of pyrimidine deoxyribonucleotides
  • de novo biosynthesis of pyrimidine ribonucleotidesribitol degradation
  • glycerol degradation I
  • phenylacetate degradation, aerobic
  • salvage pathways of adenine, hypoxanthine, and their nucleosides
  • salvage pathways of guanine, xanthine, and their nucleosides
  • salvage pathways of pyrimidine deoxyribonucleotides
  • salvage pathways of pyrimidine ribonucleotides

  The following pathways were imported from AraCyc:

  • abscisic acid biosynthesis
  • athocyanin biosynthesis
  • brassinosteroid biosynthesis
  • camalexin biosynthesis
  • carotenoid biosynthesis
  • chlorophyll biosynthesis
  • flavonoid biosynthesis
  • flavonoid biosynthesis II
  • gibberellin biosynthesis
  • indolylmethyl glucosinolate biosynthesis
  • jasmonic acid biosynthesis
  • phenylpropanoid pathway
  • polyamine biosynthesis III
  • proanthocyanidin biosynthesis from flavanols

  The following pathways were imported from MtbRvCyc:

  • mycothiol biosynthesis
  • mycothiol oxidation
  • mycothiol-dependent detoxification pathway
  • mycothiol-dependent formaldehyde detoxification

  The following existing pathways were edited extensively in MetaCyc:

  • asparagine biosynthesis II
  • dibenzo-p-dioxin degradation
  • dibenzofuran degradation
  • ethylene biosynthesis from methionine
  • lipase pathway
  • phospholipid biosynthesis II
  • orcinol degradation
  • resorcinol degradation
  • sucrose biosynthesis
  • sulfate assimilation III
  • tetrachloroethene degradation
  • ureide biosynthesis
  • ureide degradation

• 400 new chemical structures for metabolites and other small molecules have been added to MetaCyc

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Release Notes for MetaCyc Version 6.5

Released on August 30, 2002.

MetaCyc KB Statistics

Pathways	460
Reactions	4294
Enzymes	1267
Chemical Compounds	2404
Organisms	174
Citations	2718

This release contains several new changes:

• SRI has started a collaboration with TAIR (The Arabidopsis Information Resource) at the Carnegie Institution. TAIR is responsible for adding new and editing existing plant-specific pathways to MetaCyc.
• The following pathways were added since the last release. Please note they include both microbial and plant pathways.
  • anaerobic toluene degradation
  • anaerobic m-xylene degradation
  • anaerobic cyclohexane-1-carboxylate degradation
  • C4 photosynthetic carbon assimilation cycle
  • carotenoid biosynthesis
  • cutin biosynthesis
  • epicuticular wax biosynthesis
  • glycosylglyceride biosynthesis
  • lignin biosynthesis
  • nitrate assimilation pathway
  • photorespiration
  • photosynthesis, light reaction
• In addition to adding new pathways to MetaCyc, we have also edited existing ones. We have added chemical structures, enzymes, reactions, comments and literature citations to existing pathways. The following pathways have been enhanced significantly.
  • glutamate fermentation-the methylaspartate pathway
  • glutamate fermentation-the hydroxyglutarate pathway
  • methionine salvage pathway
  • anaerobic benzoyl-CoA degradation II
• Genes have been added to MetaCyc for some enzymes.

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Release Notes for MetaCyc Version 6.0

Released on February 25, 2002.

MetaCyc KB Statistics

Pathways	449
Reactions	4218
Enzymes	1147
Chemical Compounds	2339
Organisms	158
Citations	2597

New pathways in this release:

• dhurrin biosynthesis
• homoserine degradation I
• methylglyoxal catabolism
• mevalonate pathway
• proline utilization 2
• purine synthesis 2
• trehalose biosynthesis 2

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Release Notes for MetaCyc Version 5.6

Released on June 15, 2001.

MetaCyc KB Statistics

Pathways	445
Reactions	4218
Chemical Compounds	2335
Organisms	158
Citations	2383

• Each reaction in MetaCyc that has an EC number now contains WWW links to all proteins in the PIR database that have the same EC number.
• Each reaction in MetaCyc that has an EC number now contains all enzyme names associated with that EC number by the Enzyme Commission.
• The following pathways were added to MetaCyc since the last release:
  • (+)-camphor degradation
  • 2-nitropropane degradation
  • 3-methylquinoline degradation
  • 4-aminobutyrate degradation II
  • 4-nitrotoluene catabolism
  • myo-inositol degradation
  • p-cymene degradation
  • acetate fermentation
  • acetyl-CoA assimilation
  • acrylonitrile degradation
  • adamantanone catabolism
  • aldoxime metabolism
  • alkanesulfonate monooxygenase two-component system
  • anaerobic ammonium oxidation
  • anaerobic benzoate degradation
  • APS pathway of sulfate reduction
  • arsonoacetate degradation
  • atrazine catabolism II
  • atrazine catabolism III
  • betaine biosynthesis II
  • betaine biosynthesis III
  • bifidum pathway
  • bisulfite reduction
  • butanediol fermentation
  • caprolactam degradation
  • carbon tetrachloride degradation
  • cobalamin biosynthesis, aerobic pathway
  • coenzyme B biosynthesis
  • coenzyme M biosynthesis
  • cyanide degradation
  • degradation of 3-phenylpropionic acid
  • degradation of urate
  • diacetyl fermentation
  • dibenzo-p-dioxin degradation
  • dibenzofuran degradation
  • dibenzothiophene desulfurization
  • disproportionation of elemental sulfur
  • dissimilation of catechol, meta-cleavage
  • dissimilation of protocatechuate, meta-cleavage
  • ethanol-acetate fermentation
  • Formation of acetate from pyruvate
  • gallate degradation, anaerobic
  • glutamate degradation IX
  • glycolysis 2
  • heterofermentative lactate fermentation
  • homocysteine and cysteine interconversion
  • hydrogen oxidation
  • ketogluconate metabolism
  • L-sorbose metabolism
  • lysine degradation III
  • maleamate pathway
  • methionine degradation 2
  • methionine recycling
  • N-acetylneuraminate catabolism
  • nitrite oxidation
  • orcinol metabolism
  • oxidation of galena
  • oxidation of sulfide or sulfur to sulfite
  • phenylmercury acetate degradation
  • phospholipid biosynthesis II
  • phosphonoacetate metabolism
  • propionate catabolism, 2-methylcitrate cycle
  • purine fermentation
  • reductive tricarboxylic acid pathway
  • resorcinol metabolism
  • rhizobactin 1021 biosynthesis
  • RuMP cycle and formaldehyde assimilation
  • serine-isocitrate lyase pathway
  • sorbitol metabolism
  • stachydrine catabolism
  • succinate-propionate fermentation pathway
  • sulfate assimilation 2
  • sulfide oxidation
  • TCA cycle, variation 1
  • TCA cycle, variation 2
  • TCA cycle, variation 3
  • TCA cycle, variation 4
  • TCA cycle, variation 5
  • TCA cycle, variation 6
  • TCA cycle, variation 7
  • TCA cycle, variation 8
  • thiocyanate metabolism
  • threonine biosynthesis from homoserine
  • xylulose-monophosphate cycle

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Release Notes for MetaCyc Version 5.4

Released on Sept 1, 2000.

MetaCyc KB Statistics

Pathways	366
Reactions	4002
Chemical Compounds	2180
Organisms	131
Citations	604

The following new pathways are contained in this version of MetaCyc:

• ureide biosynthesis
• lipoxygenase pathway I
• threonine biosynthesis from homoserine
• nicotine degradation
• phosphonotase pathway
• 4-toluenesulfonate degradation pathway
• sophorosyloxydocosanoate degradation
• phenol degradation
• pentachlorophenol degradation pathway
• tetrachloroethene degradation pathway
• octane oxidation
• atrazine catabolism
• γ-hexachlorocyclohexane degradation pathway
• cyclohexanol oxidation
• central benzoyl-CoA pathway
• aromatic compound degradation
• 7α-dehydroxylation pathway
• 4-toluenecarboxylate degradation
• 2-aminobenzoate degradation
• 1,4-dichlorobenzene degradation pathway
• 1,2-dichloroethane degradation pathway
• sucrose biosynthesis
• acetylene degradation, anaerobic
• anaerobic oxidation of phenylalanine
• ethylene biosynthesis from methionine
• glyceraldehyde 3-phosphate catabolism
• pyruvate metabolism
• pentose phosphate pathway, Mycoplasma pneumoniae
• glucose fermentation
• carbon monoxide dehydrogenase pathway
• interconversion of arginine, ornithine and proline
• anaerobic glycolysis
• sophorosyloxydocosanoate biosynthesis
• trypanothione biosynthesis
• polyamine biosynthesis, Bacillus subtilis
• ureide degradation
• triglyceride biosynthesis
• phytoalexin biosynthesis
• galactolipid biosynthesis
• lipoxygenase pathway II
• lipases biosynthesis
• glycerol biosynthesis
• flavonoid biosynthesis
• biotin biosynthesis II
• starch and cellulose biosynthesis
• phenylalanine biosynthesis IV
• phenylalanine biosynthesis, Bacillus subtilis
• asparagine biosynthesis II
• arginine biosynthesis, Bacillus subtilis
• ectoine synthesis
• polythionate oxidation
• sulfur oxidation
• sulfur degradation II
• Fe³⁺-dependent sulfur oxidation pathway
• desulfonation of 2-aminobenzenesulfonate, benzenesulfonate and 4-toluenesulfonate
• 2-aminobenzenesulfonate desulfonation pathway
• nitroglycerin metabolism
• denitrification pathway
• oxidation of ammonia
• UDP-glucose conversion
• purine salvage, Halobacterium salinarium
• purine and pyrimidine metabolism in Mycoplasma pneumoniae

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Release Notes for MetaCyc Version 5.0

Released on June 1, 1999.

MetaCyc KB Statistics

Pathways	296
Reactions	3779
Chemical Compounds	1949
Citations	184

This first release of the MetaCyc Metabolic Encyclopedia is called version 5.0 so that its version numbers are synchronized with the version numbering of EcoCyc and of Pangea's Pathway Tools software.

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More About New Pathways Numbers

The MetaCyc Statistics by Year table is updated at each release. The discrepancy between the numbers of new pathways reported in the release notes and those computed by the software in the Statistics by Year table results from curation activities such as interconversions of some pre-existing base pathways and superpathways, deletion of pathways, splitting of some pre-existing large pathways into smaller segments and renaming of database objects.