Proposed Changes to the Enzyme List

References:

1.	Denger, K. and Cook, A.M. Racemase activity effected by two dehydrogenases in sulfolactate degradation by Chromohalobacter salexigens: purification of (S)-sulfolactate dehydrogenase. Microbiology 156 (2010) 967–974. [DOI] [PMID: 20007648]

[EC 1.1.1.310 created 2011, modified 2013]

1.1.1.347

Accepted name:

geraniol dehydrogenase (NAD⁺)

Reaction:

geraniol + NAD⁺ = geranial + NADH + H⁺

For diagram of acyclic monoterpenoid biosynthesis, click here

Other name(s):

GeDH; geoA (gene name)

Systematic name:

geraniol:NAD⁺ oxidoreductase

Comments:

The enzyme from the bacterium Castellaniella defragrans is most active in vitro with perillyl alcohol [2]. The enzyme from the prune mite Carpoglyphus lactis also acts (more slowly) on farnesol but not on nerol [1].

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG

References:

1.	Noge, K., Kato, M., Mori, N., Kataoka, M., Tanaka, C., Yamasue, Y., Nishida, R. and Kuwahara, Y. Geraniol dehydrogenase, the key enzyme in biosynthesis of the alarm pheromone, from the astigmatid mite Carpoglyphus lactis (Acari: Carpoglyphidae). FEBS J. 275 (2008) 2807–2817. [DOI] [PMID: 18422649]
2.	Lüddeke, F., Wülfing, A., Timke, M., Germer, F., Weber, J., Dikfidan, A., Rahnfeld, T., Linder, D., Meyerdierks, A. and Harder, J. Geraniol and geranial dehydrogenases induced in anaerobic monoterpene degradation by Castellaniella defragrans. Appl. Environ. Microbiol. 78 (2012) 2128–2136. [DOI] [PMID: 22286981]

[EC 1.1.1.347 created 2013]

1.1.1.348

Accepted name:

(3R)-2′-hydroxyisoflavanone reductase

Reaction:

a (4R)-4,2′-dihydroxyisoflavan + NADP⁺ = a (3R)-2′-hydroxyisoflavanone + NADPH + H⁺

For diagram of medicarpin and formononetin derivatives biosynthesis, click here

Glossary:

(3R)-vestitone = (3R)-2′,7-dihydroxy-4′-methoxyisoflavanone

Other name(s):

vestitone reductase; pterocarpin synthase (incorrect); pterocarpan synthase (incorrect)

Systematic name:

(3R)-2′-hydroxyisoflavanone:NADP⁺ 4-oxidoreductase

Comments:

This plant enzyme participates in the biosynthesis of the pterocarpan phytoalexins medicarpin, maackiain, and several forms of glyceollin. The enzyme has a strict stereo specificity for the 3R-isoflavanones.

Links to other databases:

BRENDA, EXPASY, KEGG, PDB, CAS registry number: 118477-70-6

References:

1.	Bless, W. and Barz, W. Isolation of pterocarpan synthase, the terminal enzyme of pterocarpan phytoalexin biosynthesis in cell-suspension cultures of Cicer arietinum. FEBS Lett. 235 (1988) 47–50.
2.	Guo, L., Dixon, R.A. and Paiva, N.L. Conversion of vestitone to medicarpin in alfalfa (Medicago sativa L.) is catalyzed by two independent enzymes. Identification, purification, and characterization of vestitone reductase and 7,2′-dihydroxy-4′-methoxyisoflavanol dehydratase. J. Biol. Chem. 269 (1994) 22372–22378. [PMID: 8071365]
3.	Guo, L., Dixon, R.A. and Paiva, N.L. The ‘pterocarpan synthase’ of alfalfa: association and co-induction of vestitone reductase and 7,2′-dihydroxy-4′-methoxy-isoflavanol (DMI) dehydratase, the two final enzymes in medicarpin biosynthesis. FEBS Lett. 356 (1994) 221–225. [DOI] [PMID: 7805842]
4.	Guo, L. and Paiva, N.L. Molecular cloning and expression of alfalfa (Medicago sativa L.) vestitone reductase, the penultimate enzyme in medicarpin biosynthesis. Arch. Biochem. Biophys. 320 (1995) 353–360. [DOI] [PMID: 7625843]
5.	Shao, H., Dixon, R.A. and Wang, X. Crystal structure of vestitone reductase from alfalfa (Medicago sativa L.). J. Mol. Biol. 369 (2007) 265–276. [DOI] [PMID: 17433362]

[EC 1.1.1.348 created 1992 as EC 1.1.1.246, part transferred 2013 to EC 1.1.1.348]

1.1.1.349

Accepted name:

norsolorinic acid ketoreductase

Reaction:

(1′S)-averantin + NADP⁺ = norsolorinic acid + NADPH + H⁺

For diagram of aflatoxin biosynthesis (part 1), click here

Glossary:

norsolorinic acid = 2-hexanoyl-1,3,6,8-tetrahydroxy-9,10-anthraquinone
(1′S)-averantin = 1,3,6,8-tetrahydroxy-[(1S)-2-hydroxyhexyl]-9,10-anthraquinone

Other name(s):

aflD (gene name); nor-1 (gene name)

Systematic name:

(1′S)-averantin:NADP⁺ oxidoreductase

Comments:

Involved in the synthesis of aflatoxins in the fungus Aspergillus parasiticus.

Links to other databases:

References:

1.	Yabe, K., Matsuyama, Y., Ando, Y., Nakajima, H. and Hamasaki, T. Stereochemistry during aflatoxin biosynthesis: conversion of norsolorinic acid to averufin. Appl. Environ. Microbiol. 59 (1993) 2486–2492. [PMID: 8368836]
2.	Zhou, R. and Linz, J.E. Enzymatic function of the nor-1 protein in aflatoxin biosynthesis in Aspergillus parasiticus. Appl. Environ. Microbiol. 65 (1999) 5639–5641. [PMID: 10584035]

[EC 1.1.1.349 created 2013]

1.1.1.350

Accepted name:

ureidoglycolate dehydrogenase (NAD⁺)

Reaction:

(S)-ureidoglycolate + NAD⁺ = N-carbamoyl-2-oxoglycine + NADH + H⁺

For diagram of AMP catabolism, click here

Systematic name:

(S)-ureidoglycolate:NAD⁺ oxidoreductase

Comments:

Involved in catabolism of purines. The enzyme from the bacterium Escherichia coli is specific for NAD⁺ [2]. cf. EC 1.1.1.154, ureidoglycolate dehydrogenase [NAD(P)⁺].

Links to other databases:

References:

1.	Cusa, E., Obradors, N., Baldoma, L., Badia, J. and Aguilar, J. Genetic analysis of a chromosomal region containing genes required for assimilation of allantoin nitrogen and linked glyoxylate metabolism in Escherichia coli. J. Bacteriol. 181 (1999) 7479–7484. [PMID: 10601204]
2.	Kim, M.I., Shin, I., Cho, S., Lee, J. and Rhee, S. Structural and functional insights into (S)-ureidoglycolate dehydrogenase, a metabolic branch point enzyme in nitrogen utilization. PLoS One 7:e52066 (2012). [DOI] [PMID: 23284870]

[EC 1.1.1.350 created 2013]

1.1.1.351

Accepted name:

phosphogluconate dehydrogenase [NAD(P)⁺-dependent, decarboxylating]

Reaction:

6-phospho-D-gluconate + NAD(P)⁺ = D-ribulose 5-phosphate + CO₂ + NAD(P)H + H⁺

For diagram of the early stages of the pentose-phosphate pathway, click here

Systematic name:

6-phospho-D-gluconate:NAD(P)⁺ 2-oxidoreductase (decarboxylating)

Comments:

The enzyme participates in the oxidative branch of the pentose phosphate pathway, whose main purpose is to produce reducing power and pentose for biosynthetic reactions. Unlike EC 1.1.1.44, phosphogluconate dehydrogenase (NADP⁺-dependent, decarboxylating), it is not specific for NADP⁺ and can accept both cofactors with similar efficiency. cf. EC 1.1.1.343, phosphogluconate dehydrogenase [NAD⁺-dependent, decarboxylating].

Links to other databases:

BRENDA, EXPASY, GTD, KEGG, PDB, CAS registry number: 9073-95-4

References:

1.	Ben-Bassat, A. and Goldberg, I. Purification and properties of glucose-6-phosphate dehydrogenase (NADP⁺/NAD⁺) and 6-phosphogluconate dehydrogenase (NADP⁺/NAD⁺) from methanol-grown Pseudomonas C. Biochim. Biophys. Acta 611 (1980) 1–10. [DOI] [PMID: 7350909]
2.	Stournaras, C., Maurer, P. and Kurz, G. 6-phospho-D-gluconate dehydrogenase from Pseudomonas fluorescens. Properties and subunit structure. Eur. J. Biochem. 130 (1983) 391–396. [DOI] [PMID: 6402366]
3.	Levy, H.R., Vought, V.E., Yin, X. and Adams, M.J. Identification of an arginine residue in the dual coenzyme-specific glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides that plays a key role in binding NADP⁺ but not NAD⁺. Arch. Biochem. Biophys. 326 (1996) 145–151. [DOI] [PMID: 8579362]

[EC 1.1.1.351 created 2013]

1.1.1.352

Accepted name:

5′-hydroxyaverantin dehydrogenase

Reaction:

(1) (1′S,5′S)-hydroxyaverantin + NAD⁺ = 5′-oxoaverantin + NADH + H⁺
(2) (1′S,5′R)-hydroxyaverantin + NAD⁺ = 5′-oxoaverantin + NADH + H⁺

For diagram of aflatoxin biosynthesis (part 1), click here

Glossary:

5′-oxoaverantin = 1,3,6,8-tetrahydroxy-2-[(1S)-1-hydroxy-5-oxohexyl]anthracene-9,10-dione

Other name(s):

HAVN dehydrogenase; adhA (gene name)

Systematic name:

(1′S,5′S)-hydroxyaverantin:NAD⁺ oxidoreductase

Comments:

Isolated from the aflatoxin-producing mold Aspergillus parasiticus [2]. Involved in aflatoxin biosynthesis. 5′-Oxoaverantin will spontaneously form averufin by intramolecular ketalisation. cf. EC 4.2.1.142, 5′-oxoaverantin cyclase.

Links to other databases:

References:

1.	Chang, P.K., Yu, J., Ehrlich, K.C., Boue, S.M., Montalbano, B.G., Bhatnagar, D. and Cleveland, T.E. adhA in Aspergillus parasiticus is involved in conversion of 5′-hydroxyaverantin to averufin. Appl. Environ. Microbiol. 66 (2000) 4715–4719. [DOI] [PMID: 11055914]
2.	Sakuno, E., Yabe, K. and Nakajima, H. Involvement of two cytosolic enzymes and a novel intermediate, 5′-oxoaverantin, in the pathway from 5′-hydroxyaverantin to averufin in aflatoxin biosynthesis. Appl. Environ. Microbiol. 69 (2003) 6418–6426. [DOI] [PMID: 14602595]

[EC 1.1.1.352 created 2013]

1.1.1.353

Accepted name:

versiconal hemiacetal acetate reductase

Reaction:

(1) versicolorone + NADP⁺ = 1′-hydroxyversicolorone + NADPH + H⁺
(2) versiconol acetate + NADP⁺ = versiconal hemiacetal acetate + NADPH + H⁺
(3) versiconol + NADP⁺ = versiconal + NADPH + H⁺

For diagram of aflatoxin biosynthesis (part 2), click here

Glossary:

1′-hydroxyversicolorone = (2S,3S)-2,4,6,8-tetrahydroxy-3-(3-oxobutyl)anthra[2,3-b]furan-5,10-dione
versiconal = (2S,3S)-2,4,6,8-tetrahydroxy-3-(2-hydroxyethyl)anthra[2,3-b]furan-5,10-dione
versiconal hemiacetal acetate = 2-[(2S,3S)-2,4,6,8-tetrahydroxy-5,10-dioxo-5,10-dihydroanthra[2,3-b]furan-3-yl]ethyl acetate
versiconol = 1,3,6,8-tetrahydroxy-3-[(2S)-1,4-dihydroxybutan-2-yl]anthracene-5,10-dione
versiconol acetate = (3S)-4-hydroxy-3-[1,3,6,8-tetrahydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl]butyl acetate
versicolorone = 1,3,6,8-tetrahydroxy-2-[(2S)-1-hydroxy-5-oxohexan-2-yl]anthracene-5,10-dione

Other name(s):

VHA reductase; VHA reductase I; VHA reductase II; vrdA (gene name)

Systematic name:

versiconol-acetate:NADP⁺ oxidoreductase

Comments:

Isolated from the mold Aspergillus parasiticus. Involved in a metabolic grid that leads to aflatoxin biosynthesis.

Links to other databases:

References:

1.	Matsushima, K., Ando, Y., Hamasaki, T. and Yabe, K. Purification and characterization of two versiconal hemiacetal acetate reductases involved in aflatoxin biosynthesis. Appl. Environ. Microbiol. 60 (1994) 2561–2567. [PMID: 16349333]
2.	Shima, Y., Shiina, M., Shinozawa, T., Ito, Y., Nakajima, H., Adachi, Y. and Yabe, K. Participation in aflatoxin biosynthesis by a reductase enzyme encoded by vrdA gene outside the aflatoxin gene cluster. Fungal Genet. Biol. 46 (2009) 221–231. [DOI] [PMID: 19211038]

[EC 1.1.1.353 created 2013]

1.2.99.8

Accepted name:

glyceraldehyde dehydrogenase (FAD-containing)

Reaction:

D-glyceraldehyde + H₂O + acceptor = D-glycerate + reduced acceptor

For diagram of the Entner-Doudoroff pathway, click here

Other name(s):

glyceraldehyde oxidoreductase

Systematic name:

D-glyceraldehyde:acceptor oxidoreductase (FAD-containing)

Comments:

The enzyme from the archaeon Sulfolobus acidocaldarius catalyses the oxidation of D-glyceraldehyde in the nonphosphorylative Entner-Doudoroff pathway. With 2,6-dichlorophenolindophenol as artificial electron acceptor, the enzyme shows a broad substrate range, but is most active with D-glyceraldehyde. It is not known which acceptor is utilized in vivo. The iron-sulfur protein contains FAD and molybdopterin guanine dinucleotide.

Links to other databases:

References:

Kardinahl, S., Schmidt, C.L., Hansen, T., Anemuller, S., Petersen, A. and Schafer, G. The strict molybdate-dependence of glucose-degradation by the thermoacidophile Sulfolobus acidocaldarius reveals the first crenarchaeotic molybdenum containing enzyme—an aldehyde oxidoreductase. Eur. J. Biochem. 260 (1999) 540–548. [DOI] [PMID: 10095793]

[EC 1.2.99.8 created 2013]

1.3.1.100

Accepted name:

chanoclavine-I aldehyde reductase

Reaction:

dihydrochanoclavine-I aldehyde + NADP⁺ = chanoclavine-I aldehyde + NADPH + H⁺

For diagram of fumigaclavin alkaloid biosynthesis, click here

Glossary:

chanoclavine-I aldehyde = (1E)-2-methyl-3-[(4R,5R)-4-(methylamino)-1,3,4,5-tetrahydrobenz[cd]indol-5-yl]prop-2-enal

Other name(s):

FgaOx3; easA (gene name)

Systematic name:

chanoclavine-I aldehyde:NAD⁺ oxidoreductase

Comments:

Contains FMN. The enzyme participates in the biosynthesis of fumigaclavine C, an ergot alkaloid produced by some fungi of the Trichocomaceae family. The enzyme catalyses the reduction of chanoclavine-I aldehyde to dihydrochanoclavine-I aldehyde. This hydrolyses spontaneously to form 6,8-dimethyl-6,7-didehydroergoline, which is converted to festuclavine by EC 1.5.1.44, festuclavine dehydrogenase.

Links to other databases:

References:

1.	Coyle, C.M., Cheng, J.Z., O'Connor, S.E. and Panaccione, D.G. An old yellow enzyme gene controls the branch point between Aspergillus fumigatus and Claviceps purpurea ergot alkaloid pathways. Appl. Environ. Microbiol. 76 (2010) 3898–3903. [DOI] [PMID: 20435769]
2.	Cheng, J.Z., Coyle, C.M., Panaccione, D.G. and O'Connor, S.E. A role for Old Yellow Enzyme in ergot alkaloid biosynthesis. J. Am. Chem. Soc. 132 (2010) 1776–1777. [DOI] [PMID: 20102147]
3.	Wallwey, C., Matuschek, M., Xie, X.L. and Li, S.M. Ergot alkaloid biosynthesis in Aspergillus fumigatus: Conversion of chanoclavine-I aldehyde to festuclavine by the festuclavine synthase FgaFS in the presence of the old yellow enzyme FgaOx3. Org. Biomol. Chem. 8 (2010) 3500–3508. [DOI] [PMID: 20526482]
4.	Xie, X., Wallwey, C., Matuschek, M., Steinbach, K. and Li, S.M. Formyl migration product of chanoclavine-I aldehyde in the presence of the old yellow enzyme FgaOx3 from Aspergillus fumigatus: a NMR structure elucidation. Magn. Reson. Chem. 49 (2011) 678–681. [DOI] [PMID: 21898587]

[EC 1.3.1.100 created 2013]

1.3.1.101

Accepted name:

2,3-bis-O-geranylgeranyl-sn-glycerol 1-phosphate reductase [NAD(P)H]

Reaction:

2,3-bis-(O-phytanyl)-sn-glycerol 1-phosphate + 8 NAD(P)⁺ = 2,3-bis-(O-geranylgeranyl)-sn-glycerol 1-phosphate + 8 NAD(P)H + 8 H⁺

For diagram of archaetidylserine biosynthesis, click here

Glossary:

phytanol = (7R,11R,15R)-3,7,11,15-tetramethylhexadecan-1-ol

Other name(s):

digeranylgeranylglycerophospholipid reductase; Ta0516m (gene name); DGGGPL reductase; 2,3-digeranylgeranylglycerophospholipid reductase

Systematic name:

2,3-bis-(O-phytany)l-sn-glycerol 1-phosphate:NAD(P)⁺ oxidoreductase

Comments:

A flavoprotein (FAD). The enzyme from the archaeon Thermoplasma acidophilum is involved in the biosynthesis of membrane lipids. In vivo the reaction occurs in the reverse direction with the formation of 2,3-bis-O-phytanyl-sn-glycerol 1-phosphate. cf. EC 1.3.7.11, 2,3-bis-O-geranylgeranyl-sn-glycero-phospholipid reductase.

Links to other databases:

References:

1.	Nishimura, Y. and Eguchi, T. Biosynthesis of archaeal membrane lipids: digeranylgeranylglycerophospholipid reductase of the thermoacidophilic archaeon Thermoplasma acidophilum. J. Biochem. 139 (2006) 1073–1081. [DOI] [PMID: 16788058]
2.	Nishimura, Y. and Eguchi, T. Stereochemistry of reduction in digeranylgeranylglycerophospholipid reductase involved in the biosynthesis of archaeal membrane lipids from Thermoplasma acidophilum. Bioorg. Chem. 35 (2007) 276–283. [DOI] [PMID: 17275067]
3.	Xu, Q., Eguchi, T., Mathews, I.I., Rife, C.L., Chiu, H.J., Farr, C.L., Feuerhelm, J., Jaroszewski, L., Klock, H.E., Knuth, M.W., Miller, M.D., Weekes, D., Elsliger, M.A., Deacon, A.M., Godzik, A., Lesley, S.A. and Wilson, I.A. Insights into substrate specificity of geranylgeranyl reductases revealed by the structure of digeranylgeranylglycerophospholipid reductase, an essential enzyme in the biosynthesis of archaeal membrane lipids. J. Mol. Biol. 404 (2010) 403–417. [DOI] [PMID: 20869368]

[EC 1.3.1.101 created 2013]

1.3.3.13

Accepted name:

albonoursin synthase

Reaction:

cyclo(L-leucyl-L-phenylalanyl) + 2 O₂ = albonoursin + 2 H₂O₂ (overall reaction)
(1a) cyclo(L-leucyl-L-phenylalanyl) + O₂ = cyclo[(Z)-α,β-didehydrophenylalanyl-L-leucyl] + H₂O₂
(1b) cyclo[(Z)-α,β-didehydrophenylalanyl-L-leucyl] + O₂ = albonoursin + H₂O₂

For diagram of cyclic dipeptide biosynthesis, click here

Glossary:

cyclo(L-leucyl-L-phenylalanyl) = (3S,6S)-3-benzyl-6-(2-methylpropyl)piperazine-2,5-dione
cyclo[(Z)-α,β-didehydrophenylalanyl-L-leucyl] = (3Z,6S)-3-benzylidene-6-(2-methylpropyl)piperazine-2,5-dione
albonoursin = (3Z,6Z)-3-benzylidene-6-(2-methylpropylidene)piperazine-2,5-dione

Other name(s):

cyclo(dipeptide):oxygen oxidoreductase; cyclic dipeptide oxidase; AlbA

Systematic name:

cyclo(L-leucyl-L-phenylalanyl):oxygen oxidoreductase

Comments:

A flavoprotein from the bacterium Streptomyces noursei. The enzyme can also oxidize several other cyclo dipeptides, the best being cyclo(L-tryptophyl-L-tryptophyl) and cyclo(L-phenylalanyl-L-phenylalanyl) [1,2].

Links to other databases:

References:

1.	Gondry, M., Lautru, S., Fusai, G., Meunier, G., Menez, A. and Genet, R. Cyclic dipeptide oxidase from Streptomyces noursei. Isolation, purification and partial characterization of a novel, amino acyl α,β-dehydrogenase. Eur. J. Biochem. 268 (2001) 1712–1721. [DOI] [PMID: 11248691]
2.	Lautru, S., Gondry, M., Genet, R. and Pernodet, J.L. The albonoursin gene cluster of S. noursei. Biosynthesis of diketopiperazine metabolites independent of nonribosomal peptide synthetases. Chem. Biol. 9 (2002) 1355–1364. [DOI] [PMID: 12498889]

[EC 1.3.3.13 created 2013]

*EC

1.3.7.7

Accepted name:

ferredoxin:protochlorophyllide reductase (ATP-dependent)

Reaction:

chlorophyllide a + oxidized ferredoxin + 2 ADP + 2 phosphate = protochlorophyllide a + reduced ferredoxin + 2 ATP + 2 H₂O

For diagram of chlorophyll biosynthesis (later stages), click here

Other name(s):

light-independent protochlorophyllide reductase

Systematic name:

ATP-dependent ferredoxin:protochlorophyllide-a 7,8-oxidoreductase

Comments:

Occurs in photosynthetic bacteria, cyanobacteria, green algae and gymnosperms. The enzyme catalyses trans-reduction of the D-ring of protochlorophyllide; the product has the (7S,8S)-configuration. Unlike EC 1.3.1.33 (protochlorophyllide reductase), light is not required. The enzyme contains a [4Fe-4S] cluster, and structurally resembles the Fe protein/MoFe protein complex of nitrogenase (EC 1.18.6.1), which catalyses an ATP-driven reduction.

Links to other databases:

References:

1.	Fujita, Y., Matsumoto, H., Takahashi, Y. and Matsubara, H. Identification of a nifDK-like gene (ORF467) involved in the biosynthesis of chlorophyll in the cyanobacterium Plectonema boryanum. Plant Cell Physiol. 34 (1993) 305–314. [PMID: 8199775]
2.	Nomata, J., Ogawa, T., Kitashima, M., Inoue, K. and Fujita, Y. NB-protein (BchN-BchB) of dark-operative protochlorophyllide reductase is the catalytic component containing oxygen-tolerant Fe-S clusters. FEBS Lett. 582 (2008) 1346–1350. [DOI] [PMID: 18358835]
3.	Muraki, N., Nomata, J., Ebata, K., Mizoguchi, T., Shiba, T., Tamiaki, H., Kurisu, G. and Fujita, Y. X-ray crystal structure of the light-independent protochlorophyllide reductase. Nature 465 (2010) 110–114. [DOI] [PMID: 20400946]

[EC 1.3.7.7 created 2011, modified 2013]

1.3.7.10

Transferred entry:

pentalenolactone synthase. Now EC 1.14.19.8, pentalenolactone synthase

[EC 1.3.7.10 created 2012, deleted 2013]

1.3.99.33

Accepted name:

urocanate reductase

Reaction:

dihydrourocanate + acceptor = urocanate + reduced acceptor

For diagram of histidine catabolism, click here

Glossary:

urocanate = 3-(1H-imidazol-4-yl)prop-2-enoate
dihydrourocanate = 3-(1H-imidazol-4-yl)propanoate

Other name(s):

urdA (gene name)

Systematic name:

dihydrourocanate:acceptor oxidoreductase

Comments:

The enzyme from the bacterium Shewanella oneidensis MR-1 contains a noncovalently-bound FAD and a covalently-bound FMN. It functions as part of an anaerobic electron transfer chain that utilizes urocanate as the terminal electron acceptor. The activity has been demonstrated with the artificial donor reduced methyl viologen.

Links to other databases:

References:

1.	Bogachev, A.V., Bertsova, Y.V., Bloch, D.A. and Verkhovsky, M.I. Urocanate reductase: identification of a novel anaerobic respiratory pathway in Shewanella oneidensis MR-1. Mol. Microbiol. 86 (2012) 1452–1463. [DOI] [PMID: 23078170]

[EC 1.3.99.33 created 2013]

1.3.99.34

Transferred entry:

2,3-bis-O-geranylgeranyl-sn-glycerol 1-phosphate reductase (donor). Now classified as EC 1.3.7.11, 2,3-bis-O-geranylgeranyl-sn-glycero-phospholipid reductase.

[EC 1.3.99.34 created 2013, deleted 2015]

1.5.1.47

Accepted name:

dihydromethanopterin reductase [NAD(P)⁺]

Reaction:

5,6,7,8-tetrahydromethanopterin + NAD(P)⁺ = 7,8-dihydromethanopterin + NAD(P)H + H⁺

For diagram of methanopterin biosynthesis (part 4), click here

Other name(s):

DmrA; H₂MPT reductase; 5,6,7,8-tetrahydromethanopterin 5,6-oxidoreductase; dihydromethanopterin reductase

Systematic name:

5,6,7,8-tetrahydromethanopterin:NAD(P)⁺ 5,6-oxidoreductase

Comments:

The enzyme, characterized from the bacterium Methylobacterium extorquens, is involved in biosynthesis of dephospho-tetrahydromethanopterin. The specific activity with NADH is 15% of that with NADPH at the same concentration [1]. It does not reduce 7,8-dihydrofolate (cf. EC 1.5.1.3, dihydrofolate reductase).

Links to other databases:

References:

1.	Caccamo, M.A., Malone, C.S. and Rasche, M.E. Biochemical characterization of a dihydromethanopterin reductase involved in tetrahydromethanopterin biosynthesis in Methylobacterium extorquens AM1. J. Bacteriol. 186 (2004) 2068–2073. [DOI] [PMID: 15028691]

[EC 1.5.1.47 created 2013, modified 2014]

1.6.1.2

Transferred entry:

NAD(P)⁺ transhydrogenase (Re/Si-specific). Now classified as EC 7.1.1.1, proton-translocating NAD(P)⁺ transhydrogenase

[EC 1.6.1.2 created 1986, modified 2013, deleted 2023]

*EC

1.7.1.4

Accepted name:

nitrite reductase [NAD(P)H]

Reaction:

NH₃ + 3 NAD(P)⁺ + 2 H₂O = nitrite + 3 NAD(P)H + 5 H⁺

Other name(s):

nitrite reductase (reduced nicotinamide adenine dinucleotide (phosphate)); assimilatory nitrite reductase (ambiguous); nitrite reductase [NAD(P)H₂]; NAD(P)H₂:nitrite oxidoreductase; nit-6 (gene name)

Systematic name:

ammonia:NAD(P)⁺ oxidoreductase

Comments:

An iron-sulfur flavoprotein (FAD) containing siroheme. The enzymes from the fungi Neurospora crassa [1], Emericella nidulans [2] and Candida nitratophila [4] can use either NADPH or NADH as electron donor. cf. EC 1.7.1.15, nitrite reductase (NADH).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9029-29-2

References:

1.	Nicholas, D.J.D., Medina, A. and Jones, O.T.G. A nitrite reductase from Neurospora crassa. Biochim. Biophys. Acta 37 (1960) 468–476. [PMID: 14426899]
2.	Pateman, J.A., Rever, B.M. and Cove, D.J. Genetic and biochemical studies of nitrate reduction in Aspergillus nidulans. Biochem. J. 104 (1967) 103–111. [PMID: 4382427]
3.	Rivas, J., Guerrero, M. G., Paneque, A. and Losada, M. Characterization of the nitrate-reducing system of the yeast Torulopsis nitratophila. Plant Sci. Lett. 1 (1973) 105–113.
4.	Lafferty, M.A. and Garrett, R.H. Purification and properties of the Neurospora crassa assimilatory nitrite reductase. J. Biol. Chem. 249 (1974) 7555–7567. [PMID: 4154942]
5.	Vega, J.M. and Garrett, R.H. Siroheme: a prosthetic group of the Neurospora crassa assimilatory nitrite reductase. J. Biol. Chem. 250 (1975) 7980–7989. [PMID: 126995]
6.	Greenbaum, P., Prodouz, K.N. and Garrett, R.H. Preparation and some properties of homogeneous Neurospora crassa assimilatory NADPH-nitrite reductase. Biochim. Biophys. Acta 526 (1978) 52–64. [DOI] [PMID: 150863]
7.	Prodouz, K.N. and Garrett, R.H. Neurospora crassa NAD(P)H-nitrite reductase. Studies on its composition and structure. J. Biol. Chem. 256 (1981) 9711–9717. [PMID: 6457037]
8.	Exley, G.E., Colandene, J.D. and Garrett, R.H. Molecular cloning, characterization, and nucleotide sequence of nit-6, the structural gene for nitrite reductase in Neurospora crassa. J. Bacteriol. 175 (1993) 2379–2392. [DOI] [PMID: 8096840]
9.	Colandene, J.D. and Garrett, R.H. Functional dissection and site-directed mutagenesis of the structural gene for NAD(P)H-nitrite reductase in Neurospora crassa. J. Biol. Chem. 271 (1996) 24096–24104. [DOI] [PMID: 8798648]

[EC 1.7.1.4 created 1961 as EC 1.6.6.4, transferred 2002 to EC 1.7.1.4, modified 2013]

1.7.1.15

Accepted name:

nitrite reductase (NADH)

Reaction:

NH₃ + 3 NAD⁺ + 2 H₂O = nitrite + 3 NADH + 5 H⁺

Other name(s):

nitrite reductase (reduced nicotinamide adenine dinucleotide); NADH-nitrite oxidoreductase; assimilatory nitrite reductase (ambiguous); nirB (gene name); nirD (gene name)

Systematic name:

ammonia:NAD⁺ oxidoreductase

Comments:

An iron-sulfur flavoprotein (FAD) containing siroheme. This prokaryotic enzyme is specific for NADH. In addition to catalysing the 6-electron reduction of nitrite to ammonia, the enzyme from Escherichia coli can also catalyse the 2-electron reduction of hydroxylamine to ammonia. cf. EC 1.7.1.4, nitrite reductase [NAD(P)H].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9029-29-2

References:

1.	Vega, J.M., Guerrero, M.G., Leadbetter, E. and Losada, M. Reduced nicotinamide-adenine dinucleotide-nitrite reductase from Azotobacter chroococcum. Biochem. J. 133 (1973) 701–708. [PMID: 4147887]
2.	Jackson, R.H., Cornish-Bowden, A. and Cole, J.A. Prosthetic groups of the NADH-dependent nitrite reductase from Escherichia coli K12. Biochem. J. 193 (1981) 861–867. [PMID: 7030314]
3.	Cammack, R., Jackson, R.H., Cornish-Bowden, A. and Cole, J.A. Electron-spin-resonance studies of the NADH-dependent nitrite reductase from Escherichia coli K12. Biochem. J. 207 (1982) 333–339. [PMID: 6297458]
4.	Harborne, N.R., Griffiths, L., Busby, S.J. and Cole, J.A. Transcriptional control, translation and function of the products of the five open reading frames of the Escherichia coli nir operon. Mol. Microbiol. 6 (1992) 2805–2813. [DOI] [PMID: 1435259]

[EC 1.7.1.15 created 2013]

1.13.11.74

Accepted name:

2-aminophenol 1,6-dioxygenase

Reaction:

2-aminophenol + O₂ = 2-aminomuconate 6-semialdehyde

Other name(s):

amnA (gene name); amnB (gene name); 2-aminophenol:oxygen 1,6-oxidoreductase (decyclizing)

Systematic name:

2-aminophenol:oxygen 1,6-oxidoreductase (ring-opening)

Comments:

The enzyme, a member of the nonheme-iron(II)-dependent dioxygenase family, is an extradiol-type dioxygenase that utilizes a non-heme ferrous iron to cleave the aromatic ring at the meta position (relative to the hydroxyl substituent). The enzyme also has some activity with 2-amino-5-methylphenol and 2-amino-4-methylphenol [1]. The enzyme from the bacterium Comamonas testosteroni CNB-1 also has the activity of EC 1.13.11.76, 2-amino-5-chlorophenol 1,6-dioxygenase [2].

Links to other databases:

References:

1.	Takenaka, S., Murakami, S., Shinke, R., Hatakeyama, K., Yukawa, H. and Aoki, K. Novel genes encoding 2-aminophenol 1,6-dioxygenase from Pseudomonas species AP-3 growing on 2-aminophenol and catalytic properties of the purified enzyme. J. Biol. Chem. 272 (1997) 14727–14732. [DOI] [PMID: 9169437]
2.	Wu, J.F., Sun, C.W., Jiang, C.Y., Liu, Z.P. and Liu, S.J. A novel 2-aminophenol 1,6-dioxygenase involved in the degradation of p-chloronitrobenzene by Comamonas strain CNB-1: purification, properties, genetic cloning and expression in Escherichia coli. Arch. Microbiol. 183 (2005) 1–8. [DOI] [PMID: 15580337]
3.	Li, D.F., Zhang, J.Y., Hou, Y.J., Liu, L., Hu, Y., Liu, S.J., Wang da, C. and Liu, W. Structures of aminophenol dioxygenase in complex with intermediate, product and inhibitor. Acta Crystallogr. D Biol. Crystallogr. 69 (2013) 32–43. [DOI] [PMID: 23275161]

[EC 1.13.11.74 created 2013]

1.14.11.37

Accepted name:

kanamycin B dioxygenase

Reaction:

kanamycin B + 2-oxoglutarate + O₂ = 2′-dehydrokanamycin A + succinate + NH₃ + CO₂

For diagram of kanamycin A biosynthesis, click here

Other name(s):

kanJ (gene name)

Systematic name:

kanamycin-B,2-oxoglutarate:oxygen oxidoreductase (deaminating, 2′-hydroxylating)

Comments:

Requires Fe²⁺ and ascorbate. Found in the bacterium Streptomyces kanamyceticus where it is involved in the conversion of the aminoglycoside antibiotic kanamycin B to kanamycin A.

Links to other databases:

References:

1.	Sucipto, H., Kudo, F. and Eguchi, T. The last step of kanamycin biosynthesis: unique deamination reaction catalyzed by the α-ketoglutarate-dependent nonheme iron dioxygenase KanJ and the NADPH-dependent reductase KanK. Angew. Chem. Int. Ed. Engl. 51 (2012) 3428–3431. [DOI] [PMID: 22374809]

[EC 1.14.11.37 created 2013, modified 2013]

1.14.13.86

Deleted entry:

2-hydroxyisoflavanone synthase. This enzyme was classified on the basis of an incorrect reaction. The activity is covered by EC 1.14.14.87, 2-hydroxyisoflavanone synthase

[EC 1.14.13.86 created 2004, deleted 2013]

*EC

1.14.13.136

Transferred entry:

2-hydroxyisoflavanone synthase. Now EC 1.14.14.87, 2-hydroxyisoflavanone synthase

[EC 1.14.13.136 created 2011, modified 2013, deleted 2018]

1.14.13.172

Accepted name:

salicylate 5-hydroxylase

Reaction:

salicylate + NADH + H⁺ + O₂ = 2,5-dihydroxybenzoate + NAD⁺ + H₂O

Glossary:

2,5-dihydroxybenzoate = gentisate

Other name(s):

nagG (gene name); nagH (gene name)

Systematic name:

salicylate,NADH:oxygen oxidoreductase (5-hydroxylating)

Comments:

This enzyme, which was characterized from the bacterium Ralstonia sp. U2, comprises a multicomponent system, containing a reductase that is an iron-sulfur flavoprotein (FAD; EC 1.18.1.7, ferredoxin—NAD(P)⁺ reductase), an iron-sulfur oxygenase, and ferredoxin.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB

References:

1.	Fuenmayor, S.L., Wild, M., Boyes, A.L. and Williams, P.A. A gene cluster encoding steps in conversion of naphthalene to gentisate in Pseudomonas sp. strain U2. J. Bacteriol. 180 (1998) 2522–2530. [PMID: 9573207]

[EC 1.14.13.172 created 2013]

1.14.13.173

Transferred entry:

11-oxo-β-amyrin 30-oxidase. Now EC 1.14.14.115, 11-oxo-β-amyrin 30-oxidase.

[EC 1.14.13.173 created 2013, deleted 2018]

1.14.13.174

Transferred entry:

averantin hydroxylase. Now EC 1.14.14.116, averantin hydroxylase

[EC 1.14.13.174 created 2013, deleted 2018]

1.14.13.175

Transferred entry:

aflatoxin B synthase. Now EC 1.14.14.117, aflatoxin B synthase

[EC 1.14.13.175 created 2013, deleted 2018]

1.14.13.176

Transferred entry:

tryprostatin B 6-hydroxylase. Now EC 1.14.14.118, tryprostatin B 6-hydroxylase

[EC 1.14.13.176 created 2013, deleted 2018]

1.14.15.13

Accepted name:

pulcherriminic acid synthase

Reaction:

cyclo(L-leucyl-L-leucyl) + 6 reduced ferredoxin + 3 O₂ = pulcherriminic acid + 6 oxidized ferredoxin + 4 H₂O

For diagram of cyclic dipeptide biosynthesis, click here

Glossary:

cyclo(L-leucyl-L-leucyl) = (3S,6S)-3,6-bis(2-methylpropyl)piperazine-2,5-dione
pulcherriminic acid = 2,5-dihydroxy-3,6-bis(2-methylpropyl)pyrazine bis-N-oxide

Other name(s):

cyclo-L-leucyl-L-leucyl dipeptide oxidase; CYP134A1; CypX (ambiguous)

Systematic name:

cyclo(L-leucyl-L-leucyl),reduced-ferredoxin:oxygen oxidoreductase (N-hydroxylating,aromatizing)

Comments:

A heme-thiolate (P-450) enzyme from the bacterium Bacillus subtilis. The order of events during the overall reaction is unknown. Pulcherrimic acid spontaneously forms an iron chelate with Fe(3+) to form the red pigment pulcherrimin [2].

Links to other databases:

References:

1.	MacDonald, J.C. Biosynthesis of pulcherriminic acid. Biochem. J. 96 (1965) 533–538. [PMID: 5837792]
2.	Cryle, M.J., Bell, S.G. and Schlichting, I. Structural and biochemical characterization of the cytochrome P450 CypX (CYP134A1) from Bacillus subtilis: a cyclo-L-leucyl-L-leucyl dipeptide oxidase. Biochemistry 49 (2010) 7282–7296. [DOI] [PMID: 20690619]

[EC 1.14.15.13 created 2013]

1.14.19.8

Accepted name:

pentalenolactone synthase

Reaction:

pentalenolactone F + O₂ + 2 reduced ferredoxin + 2 H⁺ = pentalenolactone + 2 oxidized ferredoxin + 2 H₂O

For diagram of pentalenolactone biosynthesis, click here

Glossary:

pentalenolactone F = (1R,4aR,6aS,9aR)-8,8-dimethyl-2-oxo-4,4a,6a,8,9-hexahydrospiro[oxirane-2,1-pentaleno[1,6a-c]pyran]-5-carboxylic acid
pentalenolactone = (1R,4aR,6aR,7S,9aS)-7,8-dimethyl-2-oxo-4,4a,6a,7-tetrahydrospiro[oxirane-2,1-pentaleno[1,6a-c]pyran]-5-carboxylic acid

Other name(s):

penM (gene name); pntM (gene name)

Systematic name:

pentalenolactone-reduced-ferredoxin:oxygen oxidoreductase (pentalenolactone-forming)

Comments:

A heme-thiolate protein (P-450). Isolated from the bacteria Streptomyces exfoliatus and Streptomyces arenae.

Links to other databases:

References:

1.	Zhu, D., Seo, M.J., Ikeda, H. and Cane, D.E. Genome mining in streptomyces. Discovery of an unprecedented P450-catalyzed oxidative rearrangement that is the final step in the biosynthesis of pentalenolactone. J. Am. Chem. Soc. 133 (2011) 2128–2131. [DOI] [PMID: 21284395]

[EC 1.14.19.8 created 2012 as EC 1.3.7.10, transferred 2013 to EC 1.14.19.8]

1.14.21.9

Transferred entry:

mycocyclosin synthase. Now EC 1.14.19.70, mycocyclosin synthase

[EC 1.14.21.9 created 2013, deleted 2018]

1.18.1.7

Accepted name:

ferredoxin—NAD(P)⁺ reductase (naphthalene dioxygenase ferredoxin-specific)

Reaction:

2 reduced [2Fe-2S] ferredoxin + NAD(P)⁺ + H⁺ = 2 oxidized [2Fe-2S] ferredoxin + NAD(P)H

Glossary:

ferredoxin

Other name(s):

NADH-ferredoxin(NAP) reductase

Systematic name:

ferredoxin:NAD(P)⁺ oxidoreductase

Comments:

The enzyme from the aerobic bacterium Ralstonia sp. U2 donates electrons to both EC 1.14.12.12, naphthalene 1,2-dioxygenase and EC 1.14.13.172, salicylate 5-hydroxylase [1]. The enzyme from Pseudomonas NCIB 9816 is specific for the ferredoxin associated with naphthalene dioxygenase; it contains FAD and a [2Fe-2S] cluster.

Links to other databases:

References:

1.	Zhou, N.Y., Al-Dulayymi, J., Baird, M.S. and Williams, P.A. Salicylate 5-hydroxylase from Ralstonia sp. strain U2: a monooxygenase with close relationships to and shared electron transport proteins with naphthalene dioxygenase. J. Bacteriol. 184 (2002) 1547–1555. [DOI] [PMID: 11872705]
2.	Haigler, B.E. and Gibson, D.T. Purification and properties of NADH-ferredoxinNAP reductase, a component of naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816. J. Bacteriol. 172 (1990) 457–464. [DOI] [PMID: 2294092]

[EC 1.18.1.7 created 2013]

1.21.3.9

Transferred entry:

dichlorochromopyrrolate synthase, now classified as EC 1.21.98.2, dichlorochromopyrrolate synthase

[EC 1.21.3.9 created 2010 as EC 4.3.1.26, transferred 2013 to EC 1.21.3.9, deleted 2016]

*EC

2.1.1.98

Accepted name:

diphthine synthase

Reaction:

3 S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] = 3 S-adenosyl-L-homocysteine + diphthine-[translation elongation factor 2] (overall reaction)
(1a) S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] = S-adenosyl-L-homocysteine + 2-[(3S)-3-carboxy-3-(methylamino)propyl]-L-histidine-[translation elongation factor 2]
(1b) S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-(methylamino)propyl]-L-histidine-[translation elongation factor 2] = S-adenosyl-L-homocysteine + 2-[(3S)-3-carboxy-3-(dimethylamino)propyl]-L-histidine-[translation elongation factor 2]
(1c) S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-(dimethylamino)propyl]-L-histidine-[translation elongation factor 2] = S-adenosyl-L-homocysteine + diphthine-[translation elongation factor 2]

For diagram of diphthamide biosynthesis, click here

Glossary:

diphthine = 2-[(3S)-3-carboxy-3-(trimethylamino)propyl]-L-histidine

Other name(s):

S-adenosyl-L-methionine:elongation factor 2 methyltransferase (ambiguous); diphthine methyltransferase (ambiguous); S-adenosyl-L-methionine:2-(3-carboxy-3-aminopropyl)-L-histidine-[translation elongation factor 2] methyltransferase; Dph5 (ambiguous)

Systematic name:

S-adenosyl-L-methionine:2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] methyltransferase (diphthine-[translation elongation factor 2]-forming)

Comments:

This archaeal enzyme produces the trimethylated product diphthine, which is converted into diphthamide by EC 6.3.1.14, diphthine—ammonia ligase. Different from the eukaryotic enzyme, which produces diphthine methyl ester (cf. EC 2.1.1.314). In the archaeon Pyrococcus horikoshii the enzyme acts on His⁶⁰⁰ of elongation factor 2.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 114514-25-9

References:

1.	Zhu, X., Kim, J., Su, X. and Lin, H. Reconstitution of diphthine synthase activity in vitro. Biochemistry 49 (2010) 9649–9657. [DOI] [PMID: 20873788]

[EC 2.1.1.98 created 1990, modified 2013, modified 2015]

*EC

2.1.1.110

Accepted name:

sterigmatocystin 8-O-methyltransferase

Reaction:

(1) S-adenosyl-L-methionine + sterigmatocystin = S-adenosyl-L-homocysteine + 8-O-methylsterigmatocystin
(2) S-adenosyl-L-methionine + dihydrosterigmatocystin = S-adenosyl-L-homocysteine + 8-O-methyldihydrosterigmatocystin

For diagram of sterigmatocystin biosynthesis, click here

Glossary:

sterigmatocystin = 3a,12c-dihydro-8-hydroxy-6-methoxyfuro[3′,2′:4,5]furo[2,3-c]xanthen-7-one
dihydrosterigmatocystin = 1,2,3a,12c-tetrahydro-8-hydroxy-6-methoxyfuro[3′,2′:4,5]furo[2,3-c]xanthen-7-one
8-O-methylsterigmatocystin = 6,8-dimethoxy-3a,12c-dihydrofuro[3′,2′:4,5]furo[2,3-c]xanthen-7-one
8-O-methyldihydrosterigmatocystin = 6,8-dimethoxy-1,2,3a,12c-tetrahydrofuro[3′,2′:4,5]furo[2,3-c]xanthen-7-one

Other name(s):

sterigmatocystin methyltransferase; O-methyltransferase II; sterigmatocystin 7-O-methyltransferase (incorrect); S-adenosyl-L-methionine:sterigmatocystin 7-O-methyltransferase (incorrect); OmtA

Systematic name:

S-adenosyl-L-methionine:sterigmatocystin 8-O-methyltransferase

Comments:

Dihydrosterigmatocystin can also act as acceptor. Involved in the biosynthesis of aflatoxins in fungi.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 116958-29-3

References:

1.	Bhatnagar, D., McCormick, S.P., Lee, L.S. and Hill, R.A. Identification of O-methylsterigmatocystin as an aflatoxin B1 and G1 precursor in Aspergillus parasiticus. Appl. Environ. Microbiol. 53 (1987) 1028–1033. [PMID: 3111363]
2.	Yabe, K., Ando, Y., Hashimoto, J. and Hamasaki, T. 2 distinct O-methyltransferases in aflatoxin biosynthesis. Appl. Environ. Microbiol. 55 (1989) 2172–2177. [PMID: 2802602]
3.	Yu, J., Cary, J.W., Bhatnagar, D., Cleveland, T.E., Keller, N.P. and Chu, F.S. Cloning and characterization of a cDNA from Aspergillus parasiticus encoding an O-methyltransferase involved in aflatoxin biosynthesis. Appl. Environ. Microbiol. 59 (1993) 3564–3571. [PMID: 8285664]
4.	Lee, L.W., Chiou, C.H. and Linz, J.E. Function of native OmtA in vivo and expression and distribution of this protein in colonies of Aspergillus parasiticus. Appl. Environ. Microbiol. 68 (2002) 5718–5727. [DOI] [PMID: 12406770]

[EC 2.1.1.110 created 1992, modified 2005, modified 2013]

*EC

2.1.1.197

Accepted name:

malonyl-[acyl-carrier protein] O-methyltransferase

Reaction:

S-adenosyl-L-methionine + malonyl-[acyl-carrier protein] = S-adenosyl-L-homocysteine + malonyl-[acyl-carrier protein] methyl ester

Other name(s):

BioC

Systematic name:

S-adenosyl-L-methionine:malonyl-[acyl-carrier protein] O-methyltransferase

Comments:

Involved in an early step of biotin biosynthesis in Gram-negative bacteria. This enzyme catalyses the transfer of a methyl group to the ω-carboxyl group of malonyl-[acyl-carrier protein] forming a methyl ester. The methyl ester is recognized by the fatty acid synthetic enzymes, which process it via the fatty acid elongation cycle to give pimelyl-[acyl-carrier-protein] methyl ester [5]. While the enzyme can also accept malonyl-CoA, it has a much higher activity with malonyl-[acyl-carrier protein] [6]

Links to other databases:

References:

1.	Del Campillo-Campbell, A., Kayajanian, G., Campbell, A. and Adhya, S. Biotin-requiring mutants of Escherichia coli K-12. J. Bacteriol. 94 (1967) 2065–2066. [PMID: 4864413]
2.	Rolfe, B. and Eisenberg, M.A. Genetic and biochemical analysis of the biotin loci of Escherichia coli K-12. J. Bacteriol. 96 (1968) 515–524. [PMID: 4877129]
3.	Otsuka, A.J., Buoncristiani, M.R., Howard, P.K., Flamm, J., Johnson, C., Yamamoto, R., Uchida, K., Cook, C., Ruppert, J. and Matsuzaki, J. The Escherichia coli biotin biosynthetic enzyme sequences predicted from the nucleotide sequence of the bio operon. J. Biol. Chem. 263 (1988) 19577–19585. [PMID: 3058702]
4.	Cleary, P.P. and Campbell, A. Deletion and complementation analysis of biotin gene cluster of Escherichia coli. J. Bacteriol. 112 (1972) 830–839. [PMID: 4563978]
5.	Lin, S., Hanson, R.E. and Cronan, J.E. Biotin synthesis begins by hijacking the fatty acid synthetic pathway. Nat. Chem. Biol. 6 (2010) 682–688. [DOI] [PMID: 20693992]
6.	Lin, S. and Cronan, J.E. The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl carrier protein, an essential step in biotin synthesis. J. Biol. Chem. 287 (2012) 37010–37020. [DOI] [PMID: 22965231]

[EC 2.1.1.197 created 2010, modified 2013]

2.1.1.269

Accepted name:

dimethylsulfoniopropionate demethylase

Reaction:

S,S-dimethyl-β-propiothetin + tetrahydrofolate = 3-(methylsulfanyl)propanoate + 5-methyltetrahydrofolate

For diagram of 3-(dimethylsulfonio)propanoate metabolism, click here

Glossary:

S,S-dimethyl-β-propiothetin = 3-(S,S-dimethylsulfonio)propanoate

Other name(s):

dmdA (gene name); dimethylsulfoniopropionate-dependent demethylase A

Systematic name:

S,S-dimethyl-β-propiothetin:tetrahydrofolate S-methyltransferase

Comments:

The enzyme from the marine bacteria Pelagibacter ubique and Ruegeria pomeroyi are specific towards S,S-dimethyl-β-propiothetin. They do not demethylate glycine-betaine [1,2].

Links to other databases:

References:

1.	Jansen, M. and Hansen, T.A. Tetrahydrofolate serves as a methyl acceptor in the demethylation of dimethylsulfoniopropionate in cell extracts of sulfate-reducing bacteria. Arch. Microbiol. 169 (1998) 84–87. [PMID: 9396840]
2.	Reisch, C.R., Moran, M.A. and Whitman, W.B. Dimethylsulfoniopropionate-dependent demethylase (DmdA) from Pelagibacter ubique and Silicibacter pomeroyi. J. Bacteriol. 190 (2008) 8018–8024. [DOI] [PMID: 18849431]
3.	Schuller, D.J., Reisch, C.R., Moran, M.A., Whitman, W.B. and Lanzilotta, W.N. Structures of dimethylsulfoniopropionate-dependent demethylase from the marine organism Pelagibacter ubique. Protein Sci. 21 (2012) 289–298. [DOI] [PMID: 22162093]

[EC 2.1.1.269 created 2013]

2.1.1.270

Accepted name:

(+)-6a-hydroxymaackiain 3-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + (+)-6a-hydroxymaackiain = S-adenosyl-L-homocysteine + (+)-pisatin

Glossary:

(+)-6a-hydroxymaackiain = (6aR,12aR)-6H-[1,3]dioxolo[5,6][1]benzofuro[3,2-c]chromene-3,6a(12aH)-diol
(+)-pisatin = (6aR,12aR)-3-methoxy-6H-[1,3]dioxolo[5,6][1]benzofuro[3,2-c]chromen-6a(12aH)-ol

Other name(s):

HM3OMT; HMM2

Systematic name:

S-adenosyl-L-methionine:(+)-6a-hydroxymaackiain 3-O-methyltransferase

Comments:

The protein from the plant Pisum sativum (garden pea) methylates (+)-6a-hydroxymaackiain at the 3-position. It also methylates 2,7,4′-trihydroxyisoflavanone on the 4′-position (cf. EC 2.1.1.212, 2,7,4-trihydroxyisoflavanone 4-O-methyltransferase) with lower activity.

Links to other databases:

References:

1.	Preisig, C.L., Matthews, D.E. and Vanetten, H.D. Purification and characterization of S-adenosyl-L-methionine:6a-hydroxymaackiain 3-O-methyltransferase from Pisum sativum. Plant Physiol. 91 (1989) 559–566. [PMID: 16667069]
2.	Wu, Q., Preisig, C.L. and VanEtten, H.D. Isolation of the cDNAs encoding (+)6a-hydroxymaackiain 3-O-methyltransferase, the terminal step for the synthesis of the phytoalexin pisatin in Pisum sativum. Plant Mol. Biol. 35 (1997) 551–560. [PMID: 9349277]
3.	Liu, C.J., Deavours, B.E., Richard, S.B., Ferrer, J.L., Blount, J.W., Huhman, D., Dixon, R.A. and Noel, J.P. Structural basis for dual functionality of isoflavonoid O-methyltransferases in the evolution of plant defense responses. Plant Cell 18 (2006) 3656–3669. [DOI] [PMID: 17172354]
4.	Akashi, T., VanEtten, H.D., Sawada, Y., Wasmann, C.C., Uchiyama, H. and Ayabe, S. Catalytic specificity of pea O-methyltransferases suggests gene duplication for (+)-pisatin biosynthesis. Phytochemistry 67 (2006) 2525–2530. [DOI] [PMID: 17067644]

[EC 2.1.1.270 created 2013]

2.1.1.271

Accepted name:

cobalt-precorrin-4 methyltransferase

Reaction:

S-adenosyl-L-methionine + cobalt-precorrin-4 = S-adenosyl-L-homocysteine + cobalt-precorrin-5A

For diagram of anaerobic corrin biosynthesis (part 1), click here

Other name(s):

CbiF; S-adenosyl-L-methionine:cobalt-precorrin-4 11-methyltransferase

Systematic name:

S-adenosyl-L-methionine:cobalt-precorrin-4 C¹¹-methyltransferase

Comments:

This enzyme, which participates in the anaerobic (early cobalt insertion) cobalamin biosynthesis pathway, catalyses the methylation of C-11 in cobalt-precorrin-4 to form cobalt-precorrin-5A. See EC 2.1.1.133, precorrin-4 C¹¹-methyltransferase, for the equivalent enzyme that participates in the aerobic cobalamin biosynthesis pathway.

Links to other databases:

References:

1.	Raux, E., Schubert, H.L., Woodcock, S.C., Wilson, K.S. and Warren, M.J. Cobalamin (vitamin B₁₂) biosynthesis^--cloning, expression and crystallisation of the Bacillus megaterium S-adenosyl-L-methionine-dependent cobalt-precorrin-4 transmethylase CbiF. Eur. J. Biochem. 254 (1998) 341–346. [DOI] [PMID: 9660189]
2.	Schubert, H.L., Wilson, K.S., Raux, E., Woodcock, S.C. and Warren, M.J. The X-ray structure of a cobalamin biosynthetic enzyme, cobalt-precorrin-4 methyltransferase. Nat. Struct. Biol. 5 (1998) 585–592. [DOI] [PMID: 9665173]
3.	Kajiwara, Y., Santander, P.J., Roessner, C.A., Perez, L.M. and Scott, A.I. Genetically engineered synthesis and structural characterization of cobalt-precorrin 5A and -5B, two new intermediates on the anaerobic pathway to vitamin B₁₂: definition of the roles of the CbiF and CbiG enzymes. J. Am. Chem. Soc. 128 (2006) 9971–9978. [DOI] [PMID: 16866557]

[EC 2.1.1.271 created 2013]

2.1.1.272

Accepted name:

cobalt-factor III methyltransferase

Reaction:

S-adenosyl-L-methionine + cobalt-factor III + reduced acceptor = S-adenosyl-L-homocysteine + cobalt-precorrin-4 + acceptor

For diagram of anaerobic corrin biosynthesis (part 1), click here

Other name(s):

CbiH₆₀ (gene name); S-adenosyl-L-methionine:cobalt-factor III 17-methyltransferase (ring contracting)

Systematic name:

S-adenosyl-L-methionine:cobalt-factor III C¹⁷-methyltransferase (ring contracting)

Comments:

Isolated from the bacterium Bacillus megaterium. The enzyme, which participates in the anaerobic (early cobalt insertion) pathway of adenosylcobalamin biosynthesis, catalyses a crucial reaction where the tetrapyrrole ring contracts as a result of methylation of C-17. Contains a [4Fe-4S] cluster. It can also convert cobalt-precorrin-3 to cobalt-precorrin-4. The reductant may be thioredoxin. See EC 2.1.1.131, precorrin-3B C¹⁷-methyltransferase, for the corresponding enzyme that participates in the aerobic cobalamin biosynthesis pathway.

Links to other databases:

References:

1.	Moore, S.J., Biedendieck, R., Lawrence, A.D., Deery, E., Howard, M.J., Rigby, S.E. and Warren, M.J. Characterization of the enzyme CbiH₆₀ involved in anaerobic ring contraction of the cobalamin (vitamin B₁₂) biosynthetic pathway. J. Biol. Chem. 288 (2013) 297–305. [DOI] [PMID: 23155054]

[EC 2.1.1.272 created 2013]

*EC

2.3.1.174

Accepted name:

3-oxoadipyl-CoA thiolase

Reaction:

succinyl-CoA + acetyl-CoA = CoA + 3-oxoadipyl-CoA

For diagram of aerobic phenylacetate catabolism, click here and for diagram of benzoate metabolism, click here

Systematic name:

succinyl-CoA:acetyl-CoA C-succinyltransferase

Comments:

The enzyme from the bacterium Escherichia coli also has the activity of EC 2.3.1.223 (3-oxo-5,6-dehydrosuberyl-CoA thiolase).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 403496-07-1

References:

1.	Kaschabek, S.R., Kuhn, B., Müller, D., Schmidt, E. and Reineke, W. Degradation of aromatics and chloroaromatics by Pseudomonas sp. strain B13: purification and characterization of 3-oxoadipate:succinyl-coenzyme A (CoA) transferase and 3-oxoadipyl-CoA thiolase. J. Bacteriol. 184 (2002) 207–215. [DOI] [PMID: 11741862]
2.	Gobel, M., Kassel-Cati, K., Schmidt, E. and Reineke, W. Degradation of aromatics and chloroaromatics by Pseudomonas sp. strain B13: cloning, characterization, and analysis of sequences encoding 3-oxoadipate:succinyl-coenzyme A (CoA) transferase and 3-oxoadipyl-CoA thiolase. J. Bacteriol. 184 (2002) 216–223. [DOI] [PMID: 11741863]
3.	Teufel, R., Mascaraque, V., Ismail, W., Voss, M., Perera, J., Eisenreich, W., Haehnel, W. and Fuchs, G. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc. Natl. Acad. Sci. USA 107 (2010) 14390–14395. [DOI] [PMID: 20660314]

[EC 2.3.1.174 created 2005, modified 2013]

*EC

2.3.1.203

Accepted name:

UDP-N-acetylbacillosamine N-acetyltransferase

Reaction:

acetyl-CoA + UDP-N-acetylbacillosamine = CoA + UDP-N,N′-diacetylbacillosamine

For diagram of legionaminic acid biosynthesis, click here

Glossary:

UDP-N-acetylbacillosamine = UDP-4-amino-4,6-dideoxy-N-acetyl-α-D-glucosamine
UDP-N,N′-diacetylbacillosamine = UDP-2,4-diacetamido-2,4,6-trideoxy-α-D-glucopyranose

Other name(s):

UDP-4-amino-4,6-dideoxy-N-acetyl-α-D-glucosamine N-acetyltransferase; pglD (gene name)

Systematic name:

acetyl-CoA:UDP-4-amino-4,6-dideoxy-N-acetyl-α-D-glucosamine N-acetyltransferase

Comments:

The product, UDP-N,N′-diacetylbacillosamine, is an intermediate in protein glycosylation pathways in several bacterial species, including N-linked glycosylation of certain L-asparagine residues in Campylobacter species [1,2] and O-linked glycosylation of certain L-serine residues in Neisseria species [3].

Links to other databases:

References:

1.	Olivier, N.B., Chen, M.M., Behr, J.R. and Imperiali, B. In vitro biosynthesis of UDP-N,N′-diacetylbacillosamine by enzymes of the Campylobacter jejuni general protein glycosylation system. Biochemistry 45 (2006) 13659–13669. [DOI] [PMID: 17087520]
2.	Rangarajan, E.S., Ruane, K.M., Sulea, T., Watson, D.C., Proteau, A., Leclerc, S., Cygler, M., Matte, A. and Young, N.M. Structure and active site residues of PglD, an N-acetyltransferase from the bacillosamine synthetic pathway required for N-glycan synthesis in Campylobacter jejuni. Biochemistry 47 (2008) 1827–1836. [DOI] [PMID: 18198901]
3.	Hartley, M.D., Morrison, M.J., Aas, F.E., Borud, B., Koomey, M. and Imperiali, B. Biochemical characterization of the O-linked glycosylation pathway in Neisseria gonorrhoeae responsible for biosynthesis of protein glycans containing N,N′-diacetylbacillosamine. Biochemistry 50 (2011) 4936–4948. [DOI] [PMID: 21542610]

[EC 2.3.1.203 created 2012, modified 2013]

2.3.1.223

Accepted name:

3-oxo-5,6-didehydrosuberyl-CoA thiolase

Reaction:

2,3-didehydroadipoyl-CoA + acetyl-CoA = CoA + 3-oxo-5,6-didehydrosuberoyl-CoA

Glossary:

2,3-didehydroadipoyl-CoA = 5-carboxypent-2-enoyl-CoA
3-oxo-5,6-didehydrosuberoyl-CoA = 7-carboxy-3-oxohept-5-enoyl-CoA

Other name(s):

paaJ (gene name)

Systematic name:

2,3-didehydroadipoyl-CoA:acetyl-CoA C-didehydroadipoyltransferase (double bond migration)

Comments:

The enzyme acts in the opposite direction. The enzymes from the bacteria Escherichia coli and Pseudomonas sp. Y2 also have the activity of EC 2.3.1.174 (3-oxoadipyl-CoA thiolase).

Links to other databases:

References:

1.	Teufel, R., Mascaraque, V., Ismail, W., Voss, M., Perera, J., Eisenreich, W., Haehnel, W. and Fuchs, G. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc. Natl. Acad. Sci. USA 107 (2010) 14390–14395. [DOI] [PMID: 20660314]

[EC 2.3.1.223 created 2013]

2.3.2.20

Accepted name:

cyclo(L-leucyl-L-phenylalanyl) synthase

Reaction:

L-leucyl-tRNA^Leu + L-phenylalanyl-tRNA^Phe = tRNA^Leu + tRNA^Phe + cyclo(L-leucyl-L-phenylalanyl)

For diagram of cyclic dipeptide biosynthesis, click here

Glossary:

cyclo(L-leucyl-L-phenylalanyl) = (3S,6S)-3-benzyl-6-(2-methylpropyl)piperazine-2,5-dione

Other name(s):

AlbC; cFL synthase

Systematic name:

L-leucyl-tRNA^Leu:L-phenylalanyl-tRNA^Phe leucyltransferase (cyclizing)

Comments:

The reaction proceeds following a ping-pong mechanism forming a covalent intermediate between an active site serine and the L-phenylalanine residue [2]. The protein, found in the bacterium Streptomyces noursei, also forms cyclo(L-phenylalanyl-L-phenylalanyl), cyclo(L-methionyl-L-phenylalanyl), cyclo(L-phenylalanyl-L-tyrosyl) and cyclo(L-methionyl-L-tyrosyl) [1].

Links to other databases:

References:

1.	Gondry, M., Sauguet, L., Belin, P., Thai, R., Amouroux, R., Tellier, C., Tuphile, K., Jacquet, M., Braud, S., Courcon, M., Masson, C., Dubois, S., Lautru, S., Lecoq, A., Hashimoto, S., Genet, R. and Pernodet, J.L. Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nat. Chem. Biol. 5 (2009) 414–420. [DOI] [PMID: 19430487]
2.	Sauguet, L., Moutiez, M., Li, Y., Belin, P., Seguin, J., Le Du, M.H., Thai, R., Masson, C., Fonvielle, M., Pernodet, J.L., Charbonnier, J.B. and Gondry, M. Cyclodipeptide synthases, a family of class-I aminoacyl-tRNA synthetase-like enzymes involved in non-ribosomal peptide synthesis. Nucleic Acids Res. 39 (2011) 4475–4489. [DOI] [PMID: 21296757]

[EC 2.3.2.20 created 2013]

2.3.2.21

Accepted name:

cyclo(L-tyrosyl-L-tyrosyl) synthase

Reaction:

2 L-tyrosyl-tRNA^Tyr = 2 tRNA^Tyr + cyclo(L-tyrosyl-L-tyrosyl)

For diagram of cyclic dipeptide biosynthesis, click here

Glossary:

cyclo(L-tyrosyl-L-tyrosyl) = (3S,6S)-3,6-bis[(4-hydroxyphenyl)methyl]piperazine-2,5-dione

Other name(s):

Rv2275 (gene name); cYY synthase; cyclodityrosine synthase

Systematic name:

L-tyrosyl-tRNA^Tyr:L-tyrosyl-tRNA^Tyr tyrosyltransferase (cyclizing)

Comments:

The reaction proceeds following a ping-pong mechanism forming a covalent intermediate between an active site serine and the first L-tyrosine residue [2]. The protein, from the bacterium Mycobacterium tuberculosis, also forms small amounts of cyclo(L-tyrosyl-L-phenylalanyl) [1].

Links to other databases:

References:

1.	Gondry, M., Sauguet, L., Belin, P., Thai, R., Amouroux, R., Tellier, C., Tuphile, K., Jacquet, M., Braud, S., Courcon, M., Masson, C., Dubois, S., Lautru, S., Lecoq, A., Hashimoto, S., Genet, R. and Pernodet, J.L. Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nat. Chem. Biol. 5 (2009) 414–420. [DOI] [PMID: 19430487]
2.	Vetting, M.W., Hegde, S.S. and Blanchard, J.S. The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase. Nat. Chem. Biol. 6 (2010) 797–799. [DOI] [PMID: 20852636]

[EC 2.3.2.21 created 2013]

2.3.2.22

Accepted name:

cyclo(L-leucyl-L-leucyl) synthase

Reaction:

2 L-leucyl-tRNA^Leu = 2 tRNA^Leu + cyclo(L-leucyl-L-leucyl)

For diagram of cyclic dipeptide biosynthesis, click here

Glossary:

cyclo(L-leucyl-L-leucyl) = (3S,6S)-3,6-bis(2-methylpropyl)piperazine-2,5-dione

Other name(s):

YvmC; cLL synthase; cyclodileucine synthase

Systematic name:

L-leucyl-tRNA^Leu:L-leucyl-tRNA^Leu leucyltransferase (cyclizing)

Comments:

The reaction proceeds following a ping-pong mechanism forming a covalent intermediate between an active site serine and the first L-leucine residue [2]. The proteins from bacteria of the genus Bacillus also form small amounts of cyclo(L-phenylalanyl-L-leucyl) and cyclo(L-leucyl-L-methionyl) [1].

Links to other databases:

References:

1.	Gondry, M., Sauguet, L., Belin, P., Thai, R., Amouroux, R., Tellier, C., Tuphile, K., Jacquet, M., Braud, S., Courcon, M., Masson, C., Dubois, S., Lautru, S., Lecoq, A., Hashimoto, S., Genet, R. and Pernodet, J.L. Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nat. Chem. Biol. 5 (2009) 414–420. [DOI] [PMID: 19430487]
2.	Bonnefond, L., Arai, T., Sakaguchi, Y., Suzuki, T., Ishitani, R. and Nureki, O. Structural basis for nonribosomal peptide synthesis by an aminoacyl-tRNA synthetase paralog. Proc. Natl. Acad. Sci. USA 108 (2011) 3912–3917. [DOI] [PMID: 21325056]

[EC 2.3.2.22 created 2013]

*EC

2.4.2.2

Accepted name:

pyrimidine-nucleoside phosphorylase

Reaction:

(1) uridine + phosphate = uracil + α-D-ribose 1-phosphate
(2) cytidine + phosphate = cytosine + α-D-ribose 1-phosphate
(3) 2′-deoxyuridine + phosphate = uracil + 2-deoxy-α-D-ribose 1-phosphate
(4) thymidine + phosphate = thymine + 2-deoxy-α-D-ribose 1-phosphate

Other name(s):

Py-NPase; pdp (gene name)

Systematic name:

pyrimidine-nucleoside:phosphate (2′-deoxy)-α-D-ribosyltransferase

Comments:

Unlike EC 2.4.2.3, uridine phosphorylase, and EC 2.4.2.4, thymidine phosphorylase, this enzyme can accept both the ribonucleosides uridine and cytidine and the 2′-deoxyribonucleosides 2′-deoxyuridine and thymidine [3,6]. The reaction is reversible, and the enzyme does not distinguish between α-D-ribose 1-phosphate and 2-deoxy-α-D-ribose 1-phosphate in the synthetic direction.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9055-35-0

References:

1.	Friedkin, M. and Kalckar, H. Nucleoside phosphorylases. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Ed.), The Enzymes, 2nd edn, vol. 5, Academic Press, New York, 1961, pp. 237–255.
2.	Saunders, P.P., Wilson, B.A. and Saunders, G.F. Purification and comparative properties of a pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus. J. Biol. Chem. 244 (1969) 3691–3697. [PMID: 4978445]
3.	Hamamoto, T., Noguchi, T. and Midorikawa, Y. Purification and characterization of purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus TH 6-2. Biosci. Biotechnol. Biochem. 60 (1996) 1179–1180. [DOI] [PMID: 8782414]
4.	Okuyama, K., Hamamoto, T., Noguchi, T. and Midorikawa, Y. Molecular cloning and expression of the pyrimidine nucleoside phosphorylase gene from Bacillus stearothermophilus TH 6-2. Biosci. Biotechnol. Biochem. 60 (1996) 1655–1659. [DOI] [PMID: 8987664]
5.	Pugmire, M.J. and Ealick, S.E. The crystal structure of pyrimidine nucleoside phosphorylase in a closed conformation. Structure 6 (1998) 1467–1479. [DOI] [PMID: 9817849]
6.	Wei, X.K., Ding, Q.B., Zhang, L., Guo, Y.L., Ou, L. and Wang, C.L. Induction of nucleoside phosphorylase in Enterobacter aerogenes and enzymatic synthesis of adenine arabinoside. J Zhejiang Univ Sci B 9 (2008) 520–526. [DOI] [PMID: 18600781]

[EC 2.4.2.2 created 1961, modified 2021]

2.4.2.11

Transferred entry:

nicotinate phosphoribosyltransferase. Now EC 6.3.4.21, nicotinate phosphoribosyltransferase.

[EC 2.4.2.11 created 1961, deleted 2013]

2.4.2.23

Transferred entry:

deoxyuridine phosphorylase. This activity has been shown to be catalysed by EC 2.4.2.2, pyrimidine-nucleoside phosphorylase, EC 2.4.2.3, uridine phosphorylase, and EC 2.4.2.4, thymidine phosphorylase.

[EC 2.4.2.23 created 1972, deleted 2013]

*EC

2.4.2.36

Accepted name:

NAD⁺—diphthamide ADP-ribosyltransferase

Reaction:

NAD⁺ + diphthamide-[translation elongation factor 2] = nicotinamide + N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2]

For diagram of diphthamide biosynthesis, click here

Glossary:

diphthamide = 2-[4-amino-4-oxo-3-(trimethylammonio)butyl]-L-histidine

Other name(s):

ADP-ribosyltransferase; mono(ADPribosyl)transferase; NAD—diphthamide ADP-ribosyltransferase; NAD⁺:peptide-diphthamide N-(ADP-D-ribosyl)transferase

Systematic name:

NAD⁺:diphthamide-[translation elongation factor 2] N-(ADP-D-ribosyl)transferase

Comments:

Diphtheria toxin and some other bacterial toxins catalyse this reaction, which inactivates translation elongation factor 2 (EF2). The acceptor is diphthamide, a unique modification of a histidine residue in the elongation factor found in archaebacteria and all eukaryotes, but not in eubacteria. cf. EC 2.4.2.31 NAD(P)⁺—protein-arginine ADP-ribosyltransferase. The relevant histidine of EF2 is His⁷¹⁵ in mammals, His⁶⁹⁹ in yeast and His⁶⁰⁰ in Pyrococcus horikoshii.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 52933-21-8

References:

1.	Lee, H. and Iglewski, W.J. Cellular ADP-ribosyltransferase with the same mechanism of action as diphtheria toxin and Pseudomonas toxin A. Proc. Natl. Acad. Sci. USA 81 (1984) 2703–2707. [DOI] [PMID: 6326138]
2.	Ueda, K. and Hayaishi, O. ADP-ribosylation. Annu. Rev. Biochem. 54 (1985) 73–100. [DOI] [PMID: 3927821]

[EC 2.4.2.36 created 1990, modified 2013]

2.4.2.52

Accepted name:

triphosphoribosyl-dephospho-CoA synthase

Reaction:

ATP + 3′-dephospho-CoA = 2′-(5-triphospho-α-D-ribosyl)-3′-dephospho-CoA + adenine

For diagram of holo-citrate-lyase biosynthesis, click here

Other name(s):

2′-(5′′-triphosphoribosyl)-3-dephospho-CoA synthase; ATP:dephospho-CoA 5-triphosphoribosyl transferase; CitG; ATP:dephospho-CoA 5′-triphosphoribosyl transferase; MdcB; ATP:3-dephospho-CoA 5′′-triphosphoribosyltransferase; MadG

Systematic name:

ATP:3′-dephospho-CoA 5-triphospho-α-D-ribosyltransferase

Comments:

ATP cannot be replaced by GTP, CTP, UTP, ADP or AMP. The reaction involves the formation of a new α (1′′→2′) glycosidic bond between the two ribosyl moieties, with concomitant displacement of the adenine moiety of ATP [1,4]. The 2′-(5-triphosphoribosyl)-3′-dephospho-CoA produced can be transferred by EC 2.7.7.61, citrate lyase holo-[acyl-carrier protein] synthase, to the apo-acyl-carrier protein subunit (γ-subunit) of EC 4.1.3.6, citrate (pro-3S) lyase, thus converting it from an apo-enzyme into a holo-enzyme [1,3]. Alternatively, it can be transferred to the apo-ACP subunit of malonate decarboxylase by the action of EC 2.7.7.66, malonate decarboxylase holo-[acyl-carrier protein] synthase [4].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 313345-38-9

References:

1.	Schneider, K., Dimroth, P. and Bott, M. Biosynthesis of the prosthetic group of citrate lyase. Biochemistry 39 (2000) 9438–9450. [DOI] [PMID: 10924139]
2.	Schneider, K., Dimroth, P. and Bott, M. Identification of triphosphoribosyl-dephospho-CoA as precursor of the citrate lyase prosthetic group. FEBS Lett. 483 (2000) 165–168. [DOI] [PMID: 11042274]
3.	Schneider, K., Kästner, C.N., Meyer, M., Wessel, M., Dimroth, P. and Bott, M. Identification of a gene cluster in Klebsiella pneumoniae which includes citX, a gene required for biosynthesis of the citrate lyase prosthetic group. J. Bacteriol. 184 (2002) 2439–2446. [DOI] [PMID: 11948157]
4.	Hoenke, S., Wild, M.R. and Dimroth, P. Biosynthesis of triphosphoribosyl-dephospho-coenzyme A, the precursor of the prosthetic group of malonate decarboxylase. Biochemistry 39 (2000) 13223–13232. [DOI] [PMID: 11052675]

[EC 2.4.2.52 created 2002 as EC 2.7.8.25, modified 2008, transferred 2013 to EC 2.4.2.52]

2.4.2.53

Accepted name:

undecaprenyl-phosphate 4-deoxy-4-formamido-L-arabinose transferase

Reaction:

UDP-4-deoxy-4-formamido-β-L-arabinopyranose + ditrans,octacis-undecaprenyl phosphate = UDP + 4-deoxy-4-formamido-α-L-arabinopyranosyl ditrans,octacis-undecaprenyl phosphate

For diagram of UDP-4-amino-4-deoxy-β-L-arabinose biosynthesis, click here

Other name(s):

undecaprenyl-phosphate Ara4FN transferase; Ara4FN transferase; polymyxin resistance protein PmrF; UDP-4-amino-4-deoxy-α-L-arabinose:ditrans,polycis-undecaprenyl phosphate 4-amino-4-deoxy-α-L-arabinosyltransferase

Systematic name:

UDP-4-amino-4-deoxy-α-L-arabinose:ditrans,octacis-undecaprenyl phosphate 4-amino-4-deoxy-α-L-arabinosyltransferase

Comments:

The enzyme shows no activity with UDP-4-amino-4-deoxy-β-L-arabinose.

Links to other databases:

References:

1.	Breazeale, S.D., Ribeiro, A.A. and Raetz, C.R. Oxidative decarboxylation of UDP-glucuronic acid in extracts of polymyxin-resistant Escherichia coli. Origin of lipid a species modified with 4-amino-4-deoxy-L-arabinose. J. Biol. Chem. 277 (2002) 2886–2896. [DOI] [PMID: 11706007]
2.	Breazeale, S.D., Ribeiro, A.A., McClerren, A.L. and Raetz, C.R.H. A formyltransferase required for polymyxin resistance in Escherichia coli and the modification of lipid A with 4-amino-4-deoxy-L-arabinose. Identification and function of UDP-4-deoxy-4-formamido-L-arabinose. J. Biol. Chem. 280 (2005) 14154–14167. [DOI] [PMID: 15695810]

[EC 2.4.2.53 created 2010 as EC 2.7.8.30, modified 2011, transferred 2013 to EC 2.4.2.53]

2.4.2.54

Accepted name:

β-ribofuranosylphenol 5′-phosphate synthase

Reaction:

5-phospho-α-D-ribose 1-diphosphate + 4-hydroxybenzoate = 4-(β-D-ribofuranosyl)phenol 5′-phosphate + CO₂ + diphosphate

For diagram of methanopterin biosynthesis (part 2), click here

Other name(s):

β-RFAP synthase (incorrect); β-RFA-P synthase (incorrect); AF2089 (gene name); MJ1427 (gene name); β-ribofuranosylhydroxybenzene 5′-phosphate synthase; 4-(β-D-ribofuranosyl)aminobenzene 5′-phosphate synthase (incorrect); β-ribofuranosylaminobenzene 5′-phosphate synthase (incorrect); 5-phospho-α-D-ribose 1-diphosphate:4-aminobenzoate 5-phospho-β-D-ribofuranosyltransferase (decarboxylating) (incorrect)

Systematic name:

5-phospho-α-D-ribose-1-diphosphate:4-hydroxybenzoate 5-phospho-β-D-ribofuranosyltransferase (decarboxylating)

Comments:

The enzyme is involved in biosynthesis of tetrahydromethanopterin in archaea. It can utilize both 4-hydroxybenzoate and 4-aminobenzoate as substrates, but only the former is known to be produced by methanogenic archaea [4]. The activity is dependent on Mg²⁺ or Mn²⁺ [1].

Links to other databases:

References:

1.	Rasche, M.E. and White, R.H. Mechanism for the enzymatic formation of 4-(β-D-ribofuranosyl)aminobenzene 5′-phosphate during the biosynthesis of methanopterin. Biochemistry 37 (1998) 11343–11351. [DOI] [PMID: 9698382]
2.	Scott, J.W. and Rasche, M.E. Purification, overproduction, and partial characterization of β-RFAP synthase, a key enzyme in the methanopterin biosynthesis pathway. J. Bacteriol. 184 (2002) 4442–4448. [DOI] [PMID: 12142414]
3.	Dumitru, R.V. and Ragsdale, S.W. Mechanism of 4-(β-D-ribofuranosyl)aminobenzene 5′-phosphate synthase, a key enzyme in the methanopterin biosynthetic pathway. J. Biol. Chem. 279 (2004) 39389–39395. [DOI] [PMID: 15262968]
4.	White, R.H. The conversion of a phenol to an aniline occurs in the biochemical formation of the 1-(4-aminophenyl)-1-deoxy-D-ribitol moiety in methanopterin. Biochemistry 50 (2011) 6041–6052. [DOI] [PMID: 21634403]
5.	Bechard, M.E., Farahani, P., Greene, D., Pham, A., Orry, A. and Rasche, M.E. Purification, kinetic characterization, and site-directed mutagenesis of Methanothermobacter thermautotrophicus RFAP synthase produced in Escherichia coli. AIMS Microbiol 5 (2019) 186–204. [DOI] [PMID: 31663056]

[EC 2.4.2.54 created 2013, modified 2014, modified 2015]

2.5.1.104

Accepted name:

N¹-aminopropylagmatine synthase

Reaction:

S-adenosyl 3-(methylsulfanyl)propylamine + agmatine = S-methyl-5′-thioadenosine + N¹-(3-aminopropyl)agmatine

For diagram of spermidine biosynthesis, click here

Glossary:

S-adenosyl 3-(methylsulfanyl)propylamine = (3-aminopropyl){[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}methylsulfonium

Other name(s):

agmatine/cadaverine aminopropyl transferase; ACAPT; PF0127 (gene name); triamine/agmatine aminopropyltransferase; SpeE (ambiguous); agmatine aminopropyltransferase; S-adenosyl 3-(methylthio)propylamine:agmatine 3-aminopropyltransferase

Systematic name:

S-adenosyl 3-(methylsulfanyl)propylamine:agmatine 3-aminopropyltransferase

Comments:

The enzyme is involved in the biosynthesis of spermidine from agmatine in some archaea and bacteria. The enzyme from the Gram-negative bacterium Thermus thermophilus accepts agmatine, spermidine and norspermidine with similar catalytic efficiency. The enzymes from the archaea Pyrococcus furiosus and Thermococcus kodakarensis prefer agmatine, but can utilize cadaverine, putrescine and propane-1,3-diamine with much lower catalytic efficiency. cf. EC 2.5.1.16, spermidine synthase, and EC 2.5.1.23, sym-norspermidine synthase.

Links to other databases:

References:

1.	Ohnuma, M., Terui, Y., Tamakoshi, M., Mitome, H., Niitsu, M., Samejima, K., Kawashima, E. and Oshima, T. N¹-aminopropylagmatine, a new polyamine produced as a key intermediate in polyamine biosynthesis of an extreme thermophile, Thermus thermophilus. J. Biol. Chem. 280 (2005) 30073–30082. [DOI] [PMID: 15983049]
2.	Cacciapuoti, G., Porcelli, M., Moretti, M.A., Sorrentino, F., Concilio, L., Zappia, V., Liu, Z.J., Tempel, W., Schubot, F., Rose, J.P., Wang, B.C., Brereton, P.S., Jenney, F.E. and Adams, M.W. The first agmatine/cadaverine aminopropyl transferase: biochemical and structural characterization of an enzyme involved in polyamine biosynthesis in the hyperthermophilic archaeon Pyrococcus furiosus. J. Bacteriol. 189 (2007) 6057–6067. [DOI] [PMID: 17545282]
3.	Morimoto, N., Fukuda, W., Nakajima, N., Masuda, T., Terui, Y., Kanai, T., Oshima, T., Imanaka, T. and Fujiwara, S. Dual biosynthesis pathway for longer-chain polyamines in the hyperthermophilic archaeon Thermococcus kodakarensis. J. Bacteriol. 192 (2010) 4991–5001. [DOI] [PMID: 20675472]
4.	Ohnuma, M., Ganbe, T., Terui, Y., Niitsu, M., Sato, T., Tanaka, N., Tamakoshi, M., Samejima, K., Kumasaka, T. and Oshima, T. Crystal structures and enzymatic properties of a triamine/agmatine aminopropyltransferase from Thermus thermophilus. J. Mol. Biol. 408 (2011) 971–986. [DOI] [PMID: 21458463]

[EC 2.5.1.104 created 2013]

2.5.1.105

Accepted name:

7,8-dihydropterin-6-yl-methyl-4-(β-D-ribofuranosyl)aminobenzene 5′-phosphate synthase

Reaction:

(7,8-dihydropterin-6-yl)methyl diphosphate + 4-(β-D-ribofuranosyl)aniline 5′-phosphate = N-[(7,8-dihydropterin-6-yl)methyl]-4-(β-D-ribofuranosyl)aniline 5′-phosphate + diphosphate

For diagram of methanopterin biosynthesis (part 2), click here

Other name(s):

MJ0301 (gene name); dihydropteroate synthase (ambiguous)

Systematic name:

(7,8-dihydropterin-6-yl)methyl-diphosphate:4-(β-D-ribofuranosyl)aniline 5′-phosphate 6-hydroxymethyl-7,8-dihydropterintransferase

Comments:

The enzyme, which has been studied in the archaeon Methanocaldococcus jannaschii, is involved in the biosynthesis of tetrahydromethanopterin.

Links to other databases:

References:

1.	Xu, H., Aurora, R., Rose, G.D. and White, R.H. Identifying two ancient enzymes in Archaea using predicted secondary structure alignment. Nat. Struct. Biol. 6 (1999) 750–754. [DOI] [PMID: 10426953]

[EC 2.5.1.105 created 2013]

2.5.1.106

Accepted name:

tryprostatin B synthase

Reaction:

prenyl diphosphate + brevianamide F = diphosphate + tryprostatin B

For diagram of fumitremorgin alkaloid biosynthesis (part 1), click here

Glossary:

brevianamide F = (3S,8aS)-3-(1H-indol-3-ylmethyl)hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
tryprostatin B = (3S,8aS)-3-{[2-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methyl}hexahydropyrrolo[1,2-a]pyrazine-1,4-dione

Other name(s):

ftmPT1 (gene name); brevianamide F prenyltransferase (ambiguous); dimethylallyl-diphosphate:brevianamide-F dimethylallyl-C-2-transferase

Systematic name:

prenyl-diphosphate:brevianamide-F prenyl-C-2-transferase

Comments:

The enzyme from the fungus Aspergillus fumigatus can also prenylate other tryptophan-containing cyclic dipeptides. Prenylation occurs mainly at C-2 [1], but also at C-3 [2]. Involved in the biosynthetic pathways of several indole alkaloids such as tryprostatins, cyclotryprostatins, spirotryprostatins, fumitremorgins and verruculogen.

Links to other databases:

References:

1.	Grundmann, A. and Li, S.M. Overproduction, purification and characterization of FtmPT1, a brevianamide F prenyltransferase from Aspergillus fumigatus. Microbiology 151 (2005) 2199–2207. [DOI] [PMID: 16000710]
2.	Wollinsky, B., Ludwig, L., Xie, X. and Li, S.M. Breaking the regioselectivity of indole prenyltransferases: identification of regular C3-prenylated hexahydropyrrolo[2,3-b]indoles as side products of the regular C2-prenyltransferase FtmPT1. Org. Biomol. Chem. 10 (2012) 9262–9270. [DOI] [PMID: 23090579]

[EC 2.5.1.106 created 2013]

2.5.1.107

Accepted name:

verruculogen prenyltransferase

Reaction:

prenyl diphosphate + verruculogen = diphosphate + fumitremorgin A

For diagram of fumitremorgin alkaloid biosynthesis (part 2), click here

Glossary:

prenyl diphosphate = dimethylallyl diphosphate
verruculogen = (5R,10S,10aR,14aS,15bS)-10,10a-dihydroxy-6-methoxy-2,2-dimethyl-5-(2-methylprop-1-en-1-yl)-1,10,10a,14,14a,15b-hexahydro-12H-3,4-dioxa-5a,11a,15a-triazacycloocta[1,2,3-lm]indeno[5,6-b]fluorene-11,15(2H,13H)-dione
fumitremorgin A = (5R,10S,10aR,14aS,15bS)-10a-hydroxy-7-methoxy-2,2-dimethyl-10-[(3-methylbut-2-en-1-yl)oxy]-5-(2-methylprop-1-en-1-yl)-1,10,10a,14,14a,15b-hexahydro-12H-3,4-dioxa-5a,11a,15a-triazacycloocta[1,2,3-lm]indeno[5,6-b]fluorene-11,15(H,13H)-dione

Other name(s):

FtmPT3; dimethylallyl-diphosphate:verruculogen dimethylallyl-O-transferase

Systematic name:

prenyl-diphosphate:verruculogen dimethylallyl-O-transferase

Comments:

Found in a number of fungi. Catalyses the last step in the biosynthetic pathway of the indole alkaloid fumitremorgin A. The enzyme from the fungus Neosartorya fischeri is also active with fumitremorgin B and 12α,13α-dihydroxyfumitremorgin C.

Links to other databases:

References:

1.	Mundt, K., Wollinsky, B., Ruan, H.L., Zhu, T. and Li, S.M. Identification of the verruculogen prenyltransferase FtmPT3 by a combination of chemical, bioinformatic and biochemical approaches. ChemBioChem 13 (2012) 2583–2592. [DOI] [PMID: 23109474]

[EC 2.5.1.107 created 2013]

*EC

2.6.1.34

Accepted name:

UDP-N-acetylbacillosamine transaminase

Reaction:

UDP-N-acetylbacillosamine + 2-oxoglutarate = UDP-2-acetamido-2,6-dideoxy-α-D-xylo-hex-4-ulose + L-glutamate

For diagram of legionaminic acid biosynthesis, click here

Glossary:

UDP-N-acetylbacillosamine = UDP-2-acetamido-4-amino-2,4,6-trideoxy-α-D-glucose = UDP-4-amino-4,6-dideoxy-N-acetyl-α-D-glucosamine

Other name(s):

uridine diphospho-4-amino-2-acetamido-2,4,6-trideoxyglucose aminotransferase; UDP-4-amino-4,6-dideoxy-N-acetyl-α-D-glucosamine transaminase; UDP-2-acetamido-4-amino-2,4,6-trideoxyglucose transaminase; pglE (gene name); UDP-2-acetamido-4-amino-2,4,6-trideoxyglucose:2-oxoglutarate aminotransferase

Systematic name:

UDP-4-amino-4,6-dideoxy-N-acetyl-α-D-glucosamine:2-oxoglutarate aminotransferase

Comments:

A pyridoxal-phosphate protein. The enzyme is involved in biosynthesis of UDP-N,N′-diacetylbacillosamine, an intermediate in protein glycosylation pathways in several bacterial species, including N-linked glycosylation of certain L-asparagine residues in Campylobacter species [2-4] and O-linked glycosylation of certain L-serine residues in Neisseria species [5].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 37277-89-7

References:

1.	Distler, J., Kaufman, B. and Roseman, S. Enzymic synthesis of a diamino sugar nucleotide by extracts of type XIV Diplococcus pneumoniae. Arch. Biochem. Biophys. 116 (1966) 466–478. [DOI] [PMID: 4381351]
2.	Olivier, N.B., Chen, M.M., Behr, J.R. and Imperiali, B. In vitro biosynthesis of UDP-N,N′-diacetylbacillosamine by enzymes of the Campylobacter jejuni general protein glycosylation system. Biochemistry 45 (2006) 13659–13669. [DOI] [PMID: 17087520]
3.	Schoenhofen, I.C., McNally, D.J., Vinogradov, E., Whitfield, D., Young, N.M., Dick, S., Wakarchuk, W.W., Brisson, J.R. and Logan, S.M. Functional characterization of dehydratase/aminotransferase pairs from Helicobacter and Campylobacter: enzymes distinguishing the pseudaminic acid and bacillosamine biosynthetic pathways. J. Biol. Chem. 281 (2006) 723–732. [DOI] [PMID: 16286454]
4.	Rangarajan, E.S., Ruane, K.M., Sulea, T., Watson, D.C., Proteau, A., Leclerc, S., Cygler, M., Matte, A. and Young, N.M. Structure and active site residues of PglD, an N-acetyltransferase from the bacillosamine synthetic pathway required for N-glycan synthesis in Campylobacter jejuni. Biochemistry 47 (2008) 1827–1836. [DOI] [PMID: 18198901]
5.	Hartley, M.D., Morrison, M.J., Aas, F.E., Borud, B., Koomey, M. and Imperiali, B. Biochemical characterization of the O-linked glycosylation pathway in Neisseria gonorrhoeae responsible for biosynthesis of protein glycans containing N,N′-diacetylbacillosamine. Biochemistry 50 (2011) 4936–4948. [DOI] [PMID: 21542610]

[EC 2.6.1.34 created 1972, modified 2013]

2.6.1.91

Deleted entry:

UDP-4-amino-4,6-dideoxy-N-acetyl-α-D-glucosamine transaminase. Identical to EC 2.6.1.34, UDP-N-acetylbacillosamine transaminase.

[EC 2.6.1.91 created 2011, deleted 2013]

2.7.1.178

Accepted name:

2-dehydro-3-deoxyglucono/galactono-kinase

Reaction:

(1) ATP + 2-dehydro-3-deoxy-D-gluconate = ADP + 2-dehydro-3-deoxy-6-phospho-D-gluconate
(2) ATP + 2-dehydro-3-deoxy-D-galactonate = ADP + 2-dehydro-3-deoxy-6-phospho-D-galactonate

For diagram of the Entner-Doudoroff pathway, click here

Other name(s):

KDG kinase (ambiguous); KDGK (ambiguous); 2-keto-3-deoxy-D-gluconate kinase (ambiguous)

Systematic name:

ATP:2-dehydro-3-deoxy-D-gluconate/2-dehydro-3-deoxy-D-galactonate 6-phosphotransferase

Comments:

The enzyme from the archaeon Sulfolobus solfataricus is involved in glucose and galactose catabolism via the branched variant of the Entner-Doudoroff pathway. It phosphorylates 2-dehydro-3-deoxy-D-gluconate and 2-dehydro-3-deoxy-D-galactonate with similar catalytic efficiency. cf. EC 2.7.1.45, 2-dehydro-3-deoxygluconokinase and EC 2.7.1.58, 2-dehydro-3-deoxygalactonokinase.

Links to other databases:

References:

1.	Lamble, H.J., Theodossis, A., Milburn, C.C., Taylor, G.L., Bull, S.D., Hough, D.W. and Danson, M.J. Promiscuity in the part-phosphorylative Entner-Doudoroff pathway of the archaeon Sulfolobus solfataricus. FEBS Lett. 579 (2005) 6865–6869. [DOI] [PMID: 16330030]
2.	Potter, J.A., Kerou, M., Lamble, H.J., Bull, S.D., Hough, D.W., Danson, M.J. and Taylor, G.L. The structure of Sulfolobus solfataricus 2-keto-3-deoxygluconate kinase. Acta Crystallogr. D Biol. Crystallogr. 64 (2008) 1283–1287. [DOI] [PMID: 19018105]
3.	Kim, S. and Lee, S.B. Characterization of Sulfolobus solfataricus 2-keto-3-deoxy-D-gluconate kinase in the modified Entner-Doudoroff pathway. Biosci. Biotechnol. Biochem. 70 (2006) 1308–1316. [DOI] [PMID: 16794308]

[EC 2.7.1.178 created 2013]

2.7.1.179

Accepted name:

kanosamine kinase

Reaction:

ATP + kanosamine = ADP + kanosamine 6-phosphate

Glossary:

kanosamine = 3-amino-3-deoxy-D-glucose

Other name(s):

rifN (gene name)

Systematic name:

ATP:kanosamine 6-phosphotransferase

Comments:

The enzyme from the bacterium Amycolatopsis mediterranei is specific for kanosamine.

Links to other databases:

References:

Arakawa, K., Muller, R., Mahmud, T., Yu, T.W. and Floss, H.G. Characterization of the early stage aminoshikimate pathway in the formation of 3-amino-5-hydroxybenzoic acid: the RifN protein specifically converts kanosamine into kanosamine 6-phosphate. J. Am. Chem. Soc. 124 (2002) 10644–10645. [DOI] [PMID: 12207505]

[EC 2.7.1.179 created 2013]

2.7.7.54

Deleted entry:

phenylalanine adenylyltransferase. The activity is part of EC 6.3.2.40, cyclopeptine synthase.

[EC 2.7.7.54 created 1989, deleted 2013]

2.7.7.55

Deleted entry:

anthranilate adenylyltransferase. The activity is part of EC 6.3.2.40, cyclopeptine synthase.

[EC 2.7.7.55 created 1989, deleted 2013]

2.7.7.85

Accepted name:

diadenylate cyclase

Reaction:

2 ATP = 2 diphosphate + cyclic di-3′,5′-adenylate

For diagram of cyclic di-3′,5′-adenylate biosynthesis and breakdown, click here

Glossary:

cyclic di-3′,5′-adenylate = c-di-AMP = c-di-adenylate = cyclic-bis(3′→5′) dimeric AMP

Other name(s):

cyclic-di-AMP synthase; dacA (gene name); disA (gene name)

Systematic name:

ATP:ATP adenylyltransferase (cyclizing)

Comments:

Cyclic di-3′,5′-adenylate is a bioactive molecule produced by some bacteria and archaea, which may function as a secondary signalling molecule [1].The intracellular bacterial pathogen Listeria monocytogenes secretes it into the host's cytosol, where it triggers a cytosolic pathway of innate immunity [2].

Links to other databases:

References:

1.	Witte, G., Hartung, S., Buttner, K. and Hopfner, K.P. Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates. Mol. Cell 30 (2008) 167–178. [DOI] [PMID: 18439896]
2.	Woodward, J.J., Iavarone, A.T. and Portnoy, D.A. c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science 328 (2010) 1703–1705. [DOI] [PMID: 20508090]

[EC 2.7.7.85 created 2013]

2.7.8.25

Transferred entry:

triphosphoribosyl-dephospho-CoA synthase. Now EC 2.4.2.52, triphosphoribosyl-dephospho-CoA synthase

[EC 2.7.8.25 created 2002, modified 2008, deleted 2013]

2.7.8.30

Transferred entry:

undecaprenyl-phosphate 4-deoxy-4-formamido-L-arabinose transferase. Now EC 2.4.2.53, undecaprenyl-phosphate 4-deoxy-4-formamido-L-arabinose transferase

[EC 2.7.8.30 created 2010, modified 2011, deleted 2013]

2.8.3.18

Accepted name:

succinyl-CoA:acetate CoA-transferase

Reaction:

succinyl-CoA + acetate = acetyl-CoA + succinate

Other name(s):

aarC (gene name); SCACT

Systematic name:

succinyl-CoA:acetate CoA-transferase

Comments:

In some bacteria the enzyme catalyses the conversion of acetate to acetyl-CoA as part of a modified tricarboxylic acid (TCA) cycle [3,5,6]. In other organisms it converts acetyl-CoA to acetate during fermentation [1,2,4,7]. In some organisms the enzyme also catalyses the activity of EC 2.8.3.27, propanoyl-CoA:succinate CoA transferase.

Links to other databases:

References:

1.	Steinbuchel, A. and Muller, M. Anaerobic pyruvate metabolism of Tritrichomonas foetus and Trichomonas vaginalis hydrogenosomes. Mol. Biochem. Parasitol. 20 (1986) 57–65. [DOI] [PMID: 3090435]
2.	Sohling, B. and Gottschalk, G. Molecular analysis of the anaerobic succinate degradation pathway in Clostridium kluyveri. J. Bacteriol. 178 (1996) 871–880. [DOI] [PMID: 8550525]
3.	Mullins, E.A., Francois, J.A. and Kappock, T.J. A specialized citric acid cycle requiring succinyl-coenzyme A (CoA):acetate CoA-transferase (AarC) confers acetic acid resistance on the acidophile Acetobacter aceti. J. Bacteriol. 190 (2008) 4933–4940. [DOI] [PMID: 18502856]
4.	van Grinsven, K.W., van Hellemond, J.J. and Tielens, A.G. Acetate:succinate CoA-transferase in the anaerobic mitochondria of Fasciola hepatica. Mol. Biochem. Parasitol. 164 (2009) 74–79. [DOI] [PMID: 19103231]
5.	Mullins, E.A. and Kappock, T.J. Crystal structures of Acetobacter aceti succinyl-coenzyme A (CoA):acetate CoA-transferase reveal specificity determinants and illustrate the mechanism used by class I CoA-transferases. Biochemistry 51 (2012) 8422–8434. [DOI] [PMID: 23030530]
6.	Kwong, W.K., Zheng, H. and Moran, N.A. Convergent evolution of a modified, acetate-driven TCA cycle in bacteria. Nat Microbiol 2:17067 (2017). [DOI] [PMID: 28452983]
7.	Zhang, B., Lingga, C., Bowman, C. and Hackmann, T.J. A new pathway for forming acetate and synthesizing ATP during fermentation in bacteria. Appl. Environ. Microbiol. 87 (2021) e0295920. [DOI] [PMID: 33931420]

[EC 2.8.3.18 created 2013, modified 2022]

3.1.1.94

Accepted name:

versiconal hemiacetal acetate esterase

Reaction:

(1) versiconal hemiacetal acetate + H₂O = versiconal + acetate
(2) versiconol acetate + H₂O = versiconol + acetate

For diagram of aflatoxin biosynthesis (part 2), click here

Glossary:

versiconal = (2S,3S)-2,4,6,8-tetrahydroxy-3-(2-hydroxyethyl)anthra[2,3-b]furan-5,10-dione
versiconal hemiacetal acetate = 2-[(2S,3S)-2,4,6,8-tetrahydroxy-5,10-dioxo-5,10-dihydroanthra[2,3-b]furan-3-yl]ethyl acetate
versiconol = 1,3,6,8-tetrahydroxy-3-[(2S)-1,4-dihydroxybutan-2-yl]anthracene-5,10-dione
versiconol acetate = (3S)-4-hydroxy-3-[1,3,6,8-tetrahydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl]butyl acetate

Other name(s):

VHA esterase

Systematic name:

versiconal-hemiacetal-acetate O-acetylhydrolase

Comments:

Isolated from the mold Aspergillus parasiticus. Involved in a metabolic grid that leads to aflatoxin biosynthesis.

Links to other databases:

References:

1.	Kusumoto, K. and Hsieh, D.P. Purification and characterization of the esterases involved in aflatoxin biosynthesis in Aspergillus parasiticus. Can. J. Microbiol. 42 (1996) 804–810. [PMID: 8776851]
2.	Chang, P.K., Yabe, K. and Yu, J. The Aspergillus parasiticus estA-encoded esterase converts versiconal hemiacetal acetate to versiconal and versiconol acetate to versiconol in aflatoxin biosynthesis. Appl. Environ. Microbiol. 70 (2004) 3593–3599. [DOI] [PMID: 15184162]

[EC 3.1.1.94 created 2013]

3.1.3.89

Accepted name:

5′-deoxynucleotidase

Reaction:

a 2′-deoxyribonucleoside 5′-monophosphate + H₂O = a 2′-deoxyribonucleoside + phosphate

Other name(s):

yfbR (gene name)

Systematic name:

2′-deoxyribonucleoside 5′-monophosphate phosphohydrolase

Comments:

The enzyme, characterized from the bacterium Escherichia coli, shows strict specificity towards deoxyribonucleoside 5′-monophosphates and does not dephosphorylate 5′-ribonucleotides or ribonucleoside 3′-monophosphates. A divalent metal cation is required for activity, with cobalt providing the highest activity.

Links to other databases:

References:

1.	Proudfoot, M., Kuznetsova, E., Brown, G., Rao, N.N., Kitagawa, M., Mori, H., Savchenko, A. and Yakunin, A.F. General enzymatic screens identify three new nucleotidases in Escherichia coli. Biochemical characterization of SurE, YfbR, and YjjG. J. Biol. Chem. 279 (2004) 54687–54694. [DOI] [PMID: 15489502]
2.	Zimmerman, M.D., Proudfoot, M., Yakunin, A. and Minor, W. Structural insight into the mechanism of substrate specificity and catalytic activity of an HD-domain phosphohydrolase: the 5′-deoxyribonucleotidase YfbR from Escherichia coli. J. Mol. Biol. 378 (2008) 215–226. [DOI] [PMID: 18353368]

[EC 3.1.3.89 created 2013]

3.1.4.56

Accepted name:

7,8-dihydroneopterin 2′,3′-cyclic phosphate phosphodiesterase

Reaction:

(1) 7,8-dihydroneopterin 2′,3′-cyclic phosphate + H₂O = 7,8-dihydroneopterin 3′-phosphate
(2) 7,8-dihydroneopterin 2′,3′-cyclic phosphate + H₂O = 7,8-dihydroneopterin 2′-phosphate

For diagram of methanopterin biosynthesis (part 1), click here

Glossary:

7,8-dihydroneopterin 2′,3′-cyclic phosphate = 2-amino-6-{(S)-hydroxy[(4R)-2-hydroxy-2-oxido-1,3,2-dioxaphospholan-4-yl]methyl}-7,8-dihydropteridin-4(1H)-one = 2-amino-6-[(1S,2R)-1,2,3-trihydroxypropyl]-7,8-dihydro-4(1H)-pteridinone 1,2-cyclic phosphate
7,8-dihydroeopterin 3′-phosphate = (2R,3S)-3-(2-amino-4-oxo-1,4,7,8-tetrahydropteridin-6-yl)-2,3-dihydroxypropyl phosphate
7,8-dihydroneopterin 2′-phosphate = (1S,2R)-1-(2-amino-4-oxo-1,4,7,8-tetrahydropteridin-6-yl)-1,3-dihydroxypropan-2-yl phosphate

Other name(s):

MptB

Systematic name:

7,8-dihydroneopterin 2′,3′-cyclic phosphate 2′/3′-phosphodiesterase

Comments:

Contains one zinc atom and one iron atom per subunit of the dodecameric enzyme. It hydrolyses 7,8-dihydroneopterin 2′,3′-cyclic phosphate, a step in tetrahydromethanopterin biosynthesis. In vitro the enzyme forms 7,8-dihydroneopterin 2′-phosphate and 7,8-dihydroneopterin 3′-phosphate at a ratio of 4:1.

Links to other databases:

References:

1.	Mashhadi, Z., Xu, H. and White, R.H. An Fe²⁺-dependent cyclic phosphodiesterase catalyzes the hydrolysis of 7,8-dihydro-D-neopterin 2′,3′-cyclic phosphate in methanopterin biosynthesis. Biochemistry 48 (2009) 9384–9392. [DOI] [PMID: 19746965]

[EC 3.1.4.56 created 2013]

3.1.6.19

Accepted name:

(R)-specific secondary-alkylsulfatase (type III)

Reaction:

an (R)-secondary-alkyl sulfate + H₂O = an (S)-secondary-alcohol + sulfate

Other name(s):

S3 secondary alkylsulphohydrolase; Pisa1; secondary alkylsulphohydrolase; (R)-specific sec-alkylsulfatase; sec-alkylsulfatase; (R)-specific secondary-alkylsulfatase; type III (R)-specific secondary-alkylsulfatase

Systematic name:

(R)-secondary-alkyl sulfate sulfohydrolase [(S)-secondary-alcohol-forming]

Comments:

Sulfatase enzymes are classified as type I, in which the key catalytic residue is 3-oxo-L-alanine, type II, which are non-heme iron-dependent dioxygenases, or type III, whose catalytic domain adopts a metallo-β-lactamase fold and binds two zinc ions as cofactors. This enzyme belongs to the type III sulfatase family. The enzyme from the bacterium Rhodococcus ruber prefers linear secondary-alkyl sulfate esters, particularly octan-2-yl, octan-3-yl, and octan-4-yl sulfates [1]. The enzyme from the bacterium Pseudomonas sp. DSM6611 utilizes a range of secondary-alkyl sulfate esters bearing aromatic, olefinic and acetylenic moieties. Hydrolysis proceeds through inversion of the configuration at the stereogenic carbon atom, resulting in perfect enantioselectivity. cf. EC 3.1.6.1, arylsulfatase (type I), and EC 1.14.11.77, alkyl sulfatase (type II).

Links to other databases:

References:

1.	Pogorevc, M. and Faber, K. Purification and characterization of an inverting stereo- and enantioselective sec-alkylsulfatase from the gram-positive bacterium Rhodococcus ruber DSM 44541. Appl. Environ. Microbiol. 69 (2003) 2810–2815. [DOI] [PMID: 12732552]
2.	Wallner, S.R., Nestl, B.M. and Faber, K. Highly enantioselective sec-alkyl sulfatase activity of Sulfolobus acidocaldarius DSM 639. Org. Lett. 6 (2004) 5009–5010. [DOI] [PMID: 15606122]
3.	Knaus, T., Schober, M., Kepplinger, B., Faccinelli, M., Pitzer, J., Faber, K., Macheroux, P. and Wagner, U. Structure and mechanism of an inverting alkylsulfatase from Pseudomonas sp. DSM6611 specific for secondary alkyl sulfates. FEBS J. 279 (2012) 4374–4384. [DOI] [PMID: 23061549]
4.	Schober, M., Knaus, T., Toesch, M., Macheroux, P., Wagner, U. and Faber, K. The substrate spectrum of the inverting sec-alkylsulfatase Pisa1. Adv. Synth. Catal. 354 (2012) 1737–1742. [DOI]

[EC 3.1.6.19 created 2013, modified 2021]

*EC

3.2.1.10

Accepted name:

oligo-1,6-glucosidase

Reaction:

Hydrolysis of (1→6)-α-D-glucosidic linkages in some oligosaccharides produced from starch and glycogen by EC 3.2.1.1 (α-amylase), and in isomaltose

Other name(s):

limit dextrinase (erroneous); isomaltase; sucrase-isomaltase; exo-oligo-1,6-glucosidase; dextrin 6α-glucanohydrolase; α-limit dextrinase; dextrin 6-glucanohydrolase; oligosaccharide α-1,6-glucohydrolase; α-methylglucosidase

Systematic name:

oligosaccharide 6-α-glucohydrolase

Comments:

This enzyme, like EC 3.2.1.33 (amylo-α-1,6-glucosidase), can release an α-1→6-linked glucose, whereas the shortest chain that can be released by EC 3.2.1.41 (pullulanase), EC 3.2.1.142 (limit dextrinase), and EC 3.2.1.68 (isoamylase) is maltose. It also hydrolyses isomaltulose (palatinose), isomaltotriose and panose, but has no action on glycogen or phosphorylase limit dextrin. The enzyme from intestinal mucosa is a single polypeptide chain that also catalyses the reaction of EC 3.2.1.48 (sucrose α-glucosidase). Differs from EC 3.2.1.33 (amylo-α-1,6-glucosidase) in its preference for short-chain substrates and in its not requiring the 6-glucosylated residue to be at a branch point, i.e. linked at both C-1 and C-4.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9032-15-9

References:

1.	Hauri, H.-P., Quaroni, A. and Isselbacher, K.J. Biogenesis of intestinal plasma membrane: posttranslational route and cleavage of sucrase-isomaltase. Proc. Natl. Acad. Sci. USA 76 (1979) 5183–5186. [DOI] [PMID: 291933]
2.	Sjöström, H., Norén, O., Christiansen, L., Wacker, H. and Semenza, G. A fully active, two-active-site, single-chain sucrase-isomaltase from pig small intestine. Implications for the biosynthesis of a mammalian integral stalked membrane protein. J. Biol. Chem. 255 (1980) 11332–11338. [PMID: 7002920]
3.	Rodriguez, I.R., Taravel, F.R. and Whelan, W.J. Characterization and function of pig intestinal sucrase-isomaltase and its separate subunits. Eur. J. Biochem. 143 (1984) 575–582. [DOI] [PMID: 6479163]
4.	Khan, N.A. and Eaton, N.R. Purification and characterization of maltase and α-methyl glucosidase from yeast. Biochim. Biophys. Acta 146 (1967) 173–180. [DOI] [PMID: 6060462]
5.	Yamamoto, K., Nakayama, A., Yamamoto, Y. and Tabata, S. Val²¹⁶ decides the substrate specificity of α-glucosidase in Saccharomyces cerevisiae. Eur. J. Biochem. 271 (2004) 3414–3420. [DOI] [PMID: 15291818]

[EC 3.2.1.10 created 1961, modified 2000, modified 2013]

*EC

3.2.1.55

Accepted name:

non-reducing end α-L-arabinofuranosidase

Reaction:

Hydrolysis of terminal non-reducing α-L-arabinofuranoside residues in α-L-arabinosides.

Other name(s):

arabinosidase (ambiguous); α-arabinosidase; α-L-arabinosidase; α-arabinofuranosidase; polysaccharide α-L-arabinofuranosidase; α-L-arabinofuranoside hydrolase; L-arabinosidase (ambiguous); α-L-arabinanase

Systematic name:

α-L-arabinofuranoside non-reducing end α-L-arabinofuranosidase

Comments:

The enzyme acts on α-L-arabinofuranosides, α-L-arabinans containing (1,3)- and/or (1,5)-linkages, arabinoxylans and arabinogalactans. Some β-galactosidases (EC 3.2.1.23) and β-D-fucosidases (EC 3.2.1.38) also hydrolyse α-L-arabinosides. cf. EC 3.2.1.185, non-reducing end β-L-arabinofuranosidase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9067-74-7

References:

1.	Tagawa, K. and Kaji, A. Preparation of L-arabinose-containing polysaccharides and the action of an α-L-arabinofuranosidase on these polysaccharides. Carbohydr. Res. 11 (1969) 293–301.
2.	Kaji, A. and Tagawa, K. Purification, crystallization and amino acid composition of α-L-arabinofuranosidase from Aspergillus niger. Biochim. Biophys. Acta 207 (1970) 456–464. [DOI] [PMID: 5452669]
3.	Kaji, A. and Yoshihara, O. Properties of purified α-L-arabinofuranosidase from Corticium rolfsii. Biochim. Biophys. Acta 250 (1971) 367–371. [DOI] [PMID: 5143344]
4.	Margolles-Clark, E., Tenkanen, M., Nakari-Setala, T. and Penttila, M. Cloning of genes encoding α-L-arabinofuranosidase and β-xylosidase from Trichoderma reesei by expression in Saccharomyces cerevisiae. Appl. Environ. Microbiol. 62 (1996) 3840–3846. [PMID: 8837440]
5.	Inacio, J.M., Correia, I.L. and de Sa-Nogueira, I. Two distinct arabinofuranosidases contribute to arabino-oligosaccharide degradation in Bacillus subtilis. Microbiology 154 (2008) 2719–2729. [DOI] [PMID: 18757805]

[EC 3.2.1.55 created 1972, modified 1976 (EC 3.2.1.79 created 1972, incorporated 1976), modified 2013]

3.2.1.185

Accepted name:

non-reducing end β-L-arabinofuranosidase

Reaction:

β-L-arabinofuranosyl-(1→2)-β-L-arabinofuranose + H₂O = 2 β-L-arabinofuranose

Other name(s):

HypBA1

Systematic name:

β-L-arabinofuranoside non-reducing end β-L-arabinofuranosidase

Comments:

The enzyme, which was identified in the bacterium Bifidobacterium longum JCM1217, removes the β-L-arabinofuranose residue from the non-reducing end of multiple substrates, including β-L-arabinofuranosyl-hydroxyproline (Ara-Hyp), Ara₂-Hyp, Ara₃-Hyp, and β-L-arabinofuranosyl-(1→2)-1-O-methyl-β-L-arabinofuranose.In the presence of 1-alkanols, the enzyme demonstrates transglycosylation activity, retaining the anomeric configuration of the arabinofuranose residue. cf. EC 3.2.1.55, non-reducing end α-L-arabinofuranosidase.

Links to other databases:

References:

1.	Fujita, K., Takashi, Y., Obuchi, E., Kitahara, K. and Suganuma, T. Characterization of a novel β-L-arabinofuranosidase in Bifidobacterium longum: functional elucidation of a DUF1680 protein family member. J. Biol. Chem. 289 (2014) 5240–5249. [DOI] [PMID: 24385433]

[EC 3.2.1.185 created 2013]

3.3.2.12

Accepted name:

oxepin-CoA hydrolase

Reaction:

2-oxepin-2(3H)-ylideneacetyl-CoA + H₂O = 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde

For diagram of aerobic phenylacetate catabolism, click here

Glossary:

oxepin-CoA = 2-oxepin-2(3H)-ylideneacetyl-CoA

Other name(s):

paaZ (gene name)

Systematic name:

2-oxepin-2(3H)-ylideneacetyl-CoA hydrolase

Comments:

The enzyme from Escherichia coli is a bifunctional fusion protein that also catalyses EC 1.2.1.91, 3-oxo-5,6-dehydrosuberyl-CoA semialdehyde dehydrogenase. Combined the two activities result in a two-step conversion of oxepin-CoA to 3-oxo-5,6-dehydrosuberyl-CoA, part of an aerobic phenylacetate degradation pathway [1,3,4]. The enzyme from Escherichia coli also exhibits enoyl-CoA hydratase activity utilizing crotonyl-CoA as a substrate [2].

Links to other databases:

References:

1.	Ferrandez, A., Minambres, B., Garcia, B., Olivera, E.R., Luengo, J.M., Garcia, J.L. and Diaz, E. Catabolism of phenylacetic acid in Escherichia coli. Characterization of a new aerobic hybrid pathway. J. Biol. Chem. 273 (1998) 25974–25986. [DOI] [PMID: 9748275]
2.	Park, S.J. and Lee, S.Y. Identification and characterization of a new enoyl coenzyme A hydratase involved in biosynthesis of medium-chain-length polyhydroxyalkanoates in recombinant Escherichia coli. J. Bacteriol. 185 (2003) 5391–5397. [DOI] [PMID: 12949091]
3.	Ismail, W., El-Said Mohamed, M., Wanner, B.L., Datsenko, K.A., Eisenreich, W., Rohdich, F., Bacher, A. and Fuchs, G. Functional genomics by NMR spectroscopy. Phenylacetate catabolism in Escherichia coli. Eur. J. Biochem. 270 (2003) 3047–3054. [DOI] [PMID: 12846838]
4.	Teufel, R., Mascaraque, V., Ismail, W., Voss, M., Perera, J., Eisenreich, W., Haehnel, W. and Fuchs, G. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc. Natl. Acad. Sci. USA 107 (2010) 14390–14395. [DOI] [PMID: 20660314]

[EC 3.3.2.12 created 2011 as EC 3.7.1.16, transferred 2013 to EC 3.3.2.12]

3.5.3.24

Accepted name:

N¹-aminopropylagmatine ureohydrolase

Reaction:

N¹-(aminopropyl)agmatine + H₂O = spermidine + urea

For diagram of spermidine biosynthesis, click here

Systematic name:

N¹-(aminopropyl)agmatine amidinohydrolase

Comments:

The enzyme, which has been characterized from the hyperthermophilic archaeon Pyrococcus kodakarensis and the thermophilic Gram-negative bacterium Thermus thermophilus, is involved in the biosynthesis of spermidine.

Links to other databases:

References:

1.	Ohnuma, M., Terui, Y., Tamakoshi, M., Mitome, H., Niitsu, M., Samejima, K., Kawashima, E. and Oshima, T. N¹-aminopropylagmatine, a new polyamine produced as a key intermediate in polyamine biosynthesis of an extreme thermophile, Thermus thermophilus. J. Biol. Chem. 280 (2005) 30073–30082. [DOI] [PMID: 15983049]
2.	Morimoto, N., Fukuda, W., Nakajima, N., Masuda, T., Terui, Y., Kanai, T., Oshima, T., Imanaka, T. and Fujiwara, S. Dual biosynthesis pathway for longer-chain polyamines in the hyperthermophilic archaeon Thermococcus kodakarensis. J. Bacteriol. 192 (2010) 4991–5001. [DOI] [PMID: 20675472]

[EC 3.5.3.24 created 2013]

*EC

3.5.4.5

Accepted name:

cytidine deaminase

Reaction:

(1) cytidine + H₂O = uridine + NH₃
(2) 2′-deoxycytidine + H₂O = 2′-deoxyuridine + NH₃

Other name(s):

cytosine nucleoside deaminase; (deoxy)cytidine deaminase; cdd (gene name); CDA (gene name)

Systematic name:

cytidine/2′-deoxycytidine aminohydrolase

Comments:

Contains zinc. Catalyses the deamination of cytidine and 2′-deoxycytidine with similar efficiencies. The enzyme, which is widely distributed among organisms, is involved in salvage of both exogenous and endogenous cytidine and 2′-deoxycytidine for UMP synthesis.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9025-06-3

References:

1.	Roberts, D.W.A. The wheat leaf phosphatases. II. Pathway of hydrolysis of some nucleotides at pH 5.5. J. Biol. Chem. 222 (1956) 259–270. [PMID: 13366999]
2.	Wang, T.P., Sable, H.Z. and Lampen, J.O. Enzymatic deamination of cytosine nucleosides. J. Biol. Chem. 184 (1950) 17–28. [PMID: 15421968]
3.	Song, B.H. and Neuhard, J. Chromosomal location, cloning and nucleotide sequence of the Bacillus subtilis cdd gene encoding cytidine/deoxycytidine deaminase. Mol. Gen. Genet. 216 (1989) 462–468. [PMID: 2526291]
4.	Laliberte, J. and Momparler, R.L. Human cytidine deaminase: purification of enzyme, cloning, and expression of its complementary DNA. Cancer Res. 54 (1994) 5401–5407. [PMID: 7923172]
5.	Vincenzetti, S., Cambi, A., Neuhard, J., Schnorr, K., Grelloni, M. and Vita, A. Cloning, expression, and purification of cytidine deaminase from Arabidopsis thaliana. Protein Expr. Purif. 15 (1999) 8–15. [DOI] [PMID: 10024464]

[EC 3.5.4.5 created 1961, modified 2013]

3.5.4.14

Transferred entry:

deoxycytidine deaminase. Now included in EC 3.5.4.5, (deoxy)cytidine deaminase

[EC 3.5.4.14 created 1972, transferred 2013 to EC 3.5.4.5., deleted 2013]

3.5.4.37

Accepted name:

double-stranded RNA adenine deaminase

Reaction:

adenine in double-stranded RNA + H₂O = hypoxanthine in double-stranded RNA + NH₃

Other name(s):

ADAR; double-stranded RNA adenosine deaminase; dsRAD; dsRNA adenosine deaminase; DRADA1; double-stranded RNA-specific adenosine deaminase

Systematic name:

double-stranded RNA adenine aminohydrolase

Comments:

This eukaryotic enzyme is involved in RNA editing. It destabilizes double-stranded RNA through conversion of adenosine to inosine. Inositol hexakisphosphate is required for activity [4].

Links to other databases:

References:

1.	Hough, R.F. and Bass, B.L. Purification of the Xenopus laevis double-stranded RNA adenosine deaminase. J. Biol. Chem. 269 (1994) 9933–9939. [PMID: 8144588]
2.	O'Connell, M.A., Gerber, A. and Keegan, L.P. Purification of native and recombinant double-stranded RNA-specific adenosine deaminases. Methods 15 (1998) 51–62. [DOI] [PMID: 9614652]
3.	Wong, S.K., Sato, S. and Lazinski, D.W. Substrate recognition by ADAR1 and ADAR2. RNA 7 (2001) 846–858. [PMID: 11421361]
4.	Macbeth, M.R., Schubert, H.L., Vandemark, A.P., Lingam, A.T., Hill, C.P. and Bass, B.L. Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science 309 (2005) 1534–1539. [DOI] [PMID: 16141067]

[EC 3.5.4.37 created 2013]

3.5.4.38

Accepted name:

single-stranded DNA cytosine deaminase

Reaction:

cytosine in single-stranded DNA + H₂O = uracil in single-stranded DNA + NH₃

Other name(s):

AID; activation-induced deaminase; AICDA (gene name); activation-induced cytidine deaminase

Systematic name:

single-stranded DNA cytosine aminohydrolase

Comments:

The enzyme exclusively catalyses deamination of cytosine in single-stranded DNA. It preferentially deaminates five-nucleotide bubbles. The optimal target consists of a single-stranded NWRCN motif (W = A or T, R = A or G) [2]. The enzyme initiates antibody diversification processes by deaminating immunoglobulin sequences.

Links to other databases:

References:

1.	Sohail, A., Klapacz, J., Samaranayake, M., Ullah, A. and Bhagwat, A.S. Human activation-induced cytidine deaminase causes transcription-dependent, strand-biased C to U deaminations. Nucleic Acids Res. 31 (2003) 2990–2994. [PMID: 12799424]
2.	Larijani, M., Petrov, A.P., Kolenchenko, O., Berru, M., Krylov, S.N. and Martin, A. AID associates with single-stranded DNA with high affinity and a long complex half-life in a sequence-independent manner. Mol. Cell Biol. 27 (2007) 20–30. [DOI] [PMID: 17060445]
3.	Brar, S.S., Sacho, E.J., Tessmer, I., Croteau, D.L., Erie, D.A. and Diaz, M. Activation-induced deaminase, AID, is catalytically active as a monomer on single-stranded DNA. DNA Repair (Amst.) 7 (2008) 77–87. [DOI] [PMID: 17889624]
4.	Larijani, M. and Martin, A. Single-stranded DNA structure and positional context of the target cytidine determine the enzymatic efficiency of AID. Mol. Cell Biol. 27 (2007) 8038–8048. [DOI] [PMID: 17893327]
5.	Verma, S., Goldammer, T. and Aitken, R. Cloning and expression of activation induced cytidine deaminase from Bos taurus. Vet. Immunol. Immunopathol. 134 (2010) 151–159. [DOI] [PMID: 19766322]

[EC 3.5.4.38 created 2013]

3.5.4.39

Accepted name:

GTP cyclohydrolase IV

Reaction:

GTP + H₂O = 7,8-dihydroneopterin 2′,3′-cyclic phosphate + formate + diphosphate

For diagram of methanopterin biosynthesis (part 1), click here

Glossary:

Other name(s):

MptA; GTP cyclohydrolase MptA

Systematic name:

GTP 7,8-8,9-dihydrolase (cyclizing, formate-releasing, diphosphate-releasing)

Comments:

Requires Fe²⁺. A zinc protein. The enzyme is involved in methanopterin biosynthesis in methanogenic archaea. cf. GTP cyclohydrolase I (EC 3.5.4.16), GTP cyclohydrolase II (EC 3.5.4.25) and GTP cyclohydrolase IIa (EC 3.5.4.29).

Links to other databases:

References:

1.	Grochowski, L.L., Xu, H., Leung, K. and White, R.H. Characterization of an Fe²⁺-dependent archaeal-specific GTP cyclohydrolase, MptA, from Methanocaldococcus jannaschii. Biochemistry 46 (2007) 6658–6667. [DOI] [PMID: 17497938]

[EC 3.5.4.39 created 2013]

*EC

3.6.1.59

Accepted name:

5′-(N⁷-methyl 5′-triphosphoguanosine)-[mRNA] diphosphatase

Reaction:

a 5′-(N⁷-methyl 5′-triphosphoguanosine)-[mRNA] + H₂O = N⁷-methylguanosine 5′-phosphate + a 5′-diphospho-[mRNA]

Other name(s):

DcpS; m⁷GpppX pyrophosphatase; m⁷GpppN m⁷GMP phosphohydrolase; m⁷GpppX diphosphatase; m⁷G5′ppp5’N m⁷GMP phosphohydrolase

Systematic name:

5′-(N⁷-methyl 5′-triphosphoguanosine)-[mRNA] N⁷-methylguanosine 5′-phosphate phosphohydrolase

Comments:

The enzyme removes (decaps) the N⁷-methylguanosine 5-phosphate cap from an mRNA degraded to a maximal length of 10 nucleotides [3,6]. Decapping is an important process in the control of eukaryotic mRNA degradation. The enzyme functions to clear the cell of cap structure following decay of the RNA body [2]. The nematode enzyme can also decap triply methylated substrates, 5′-(N²,N²,N⁷-trimethyl 5′-triphosphoguanosine)-[mRNA] [4].

Links to other databases:

References:

1.	Malys, N. and McCarthy, J.E. Dcs2, a novel stress-induced modulator of m⁷GpppX pyrophosphatase activity that locates to P bodies. J. Mol. Biol. 363 (2006) 370–382. [DOI] [PMID: 16963086]
2.	Liu, S.W., Rajagopal, V., Patel, S.S. and Kiledjian, M. Mechanistic and kinetic analysis of the DcpS scavenger decapping enzyme. J. Biol. Chem. 283 (2008) 16427–16436. [DOI] [PMID: 18441014]
3.	Liu, H., Rodgers, N.D., Jiao, X. and Kiledjian, M. The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases. EMBO J. 21 (2002) 4699–4708. [DOI] [PMID: 12198172]
4.	van Dijk, E., Le Hir, H. and Seraphin, B. DcpS can act in the 5′-3′ mRNA decay pathway in addition to the 3′-5′ pathway. Proc. Natl. Acad. Sci. USA 100 (2003) 12081–12086. [DOI] [PMID: 14523240]
5.	Chen, N., Walsh, M.A., Liu, Y., Parker, R. and Song, H. Crystal structures of human DcpS in ligand-free and m⁷GDP-bound forms suggest a dynamic mechanism for scavenger mRNA decapping. J. Mol. Biol. 347 (2005) 707–718. [DOI] [PMID: 15769464]
6.	Cohen, L.S., Mikhli, C., Friedman, C., Jankowska-Anyszka, M., Stepinski, J., Darzynkiewicz, E. and Davis, R.E. Nematode m⁷GpppG and m3(2,2,7)GpppG decapping: activities in Ascaris embryos and characterization of C. elegans scavenger DcpS. RNA 10 (2004) 1609–1624. [DOI] [PMID: 15383679]
7.	Wypijewska, A., Bojarska, E., Lukaszewicz, M., Stepinski, J., Jemielity, J., Davis, R.E. and Darzynkiewicz, E. 7-Methylguanosine diphosphate (m⁷GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity. Biochemistry 51 (2012) 8003–8013. [DOI] [PMID: 22985415]

[EC 3.6.1.59 created 2012, modified 2013]

3.6.1.65

Accepted name:

(d)CTP diphosphatase

Reaction:

(1) CTP + H₂O = CMP + diphosphate
(2) dCTP + H₂O = dCMP + diphosphate

Other name(s):

(d)CTP pyrophosphohydrolase; (d)CTP diphosphohydrolase; nudG (gene name)

Systematic name:

(deoxy)cytidine 5′-triphosphate diphosphohydrolase

Comments:

The enzyme, characterized from the bacterium Escherichia coli, is specific for the pyrimidine nucleotides CTP and dCTP. It also acts on 5-methyl-dCTP, 5-hydroxy-dCTP and 8-hydroxy-dGTP.

Links to other databases:

References:

1.	O'Handley, S.F., Dunn, C.A. and Bessman, M.J. Orf135 from Escherichia coli is a Nudix hydrolase specific for CTP, dCTP, and 5-methyl-dCTP. J. Biol. Chem. 276 (2001) 5421–5426. [DOI] [PMID: 11053429]
2.	Fujikawa, K. and Kasai, H. The oxidized pyrimidine ribonucleotide, 5-hydroxy-CTP, is hydrolyzed efficiently by the Escherichia coli recombinant Orf135 protein. DNA Repair (Amst.) 1 (2002) 571–576. [DOI] [PMID: 12509230]
3.	Kamiya, H., Iida, E. and Harashima, H. Important amino acids in the phosphohydrolase module of Escherichia coli Orf135. Biochem. Biophys. Res. Commun. 323 (2004) 1063–1068. [DOI] [PMID: 15381107]
4.	Iida, E., Satou, K., Mishima, M., Kojima, C., Harashima, H. and Kamiya, H. Amino acid residues involved in substrate recognition of the Escherichia coli Orf135 protein. Biochemistry 44 (2005) 5683–5689. [DOI] [PMID: 15823026]

[EC 3.6.1.65 created 2013]

3.7.1.15

Transferred entry:

(+)-caryolan-1-ol synthase. Now EC 4.2.1.138, (+)-caryolan-1-ol synthase

[EC 3.7.1.15 created 2011, deleted 2013]

3.7.1.16

Transferred entry:

oxepin-CoA hydrolase. Now EC 3.3.2.12, oxepin-CoA hydrolase

[EC 3.7.1.16 created 2011, deleted 2013]

4.1.2.51

Accepted name:

2-dehydro-3-deoxy-D-gluconate aldolase

Reaction:

2-dehydro-3-deoxy-D-gluconate = pyruvate + D-glyceraldehyde

For diagram of the Entner-Doudoroff pathway, click here

Other name(s):

Pto1279 (gene name); KDGA; KDG-specific aldolase

Systematic name:

2-dehydro-3-deoxy-D-gluconate D-glyceraldehyde-lyase (pyruvate-forming)

Comments:

The enzyme from the archaeon Picrophilus torridus is involved in D-glucose and D-galactose catabolism via the nonphosphorylative variant of the Entner-Doudoroff pathway. In the direction of aldol synthesis the enzyme catalyses the formation of 2-dehydro-3-deoxy-D-gluconate and 2-dehydro-3-deoxy-D-galactonate at a similar ratio. It shows no activity with 2-dehydro-3-deoxy-D-gluconate 6-phosphate. cf. EC 4.1.2.14, 2-dehydro-3-deoxy-phosphogluconate aldolase.

Links to other databases:

References:

1.	Reher, M., Fuhrer, T., Bott, M. and Schonheit, P. The nonphosphorylative Entner-Doudoroff pathway in the thermoacidophilic euryarchaeon Picrophilus torridus involves a novel 2-keto-3-deoxygluconate- specific aldolase. J. Bacteriol. 192 (2010) 964–974. [DOI] [PMID: 20023024]

[EC 4.1.2.51 created 2013]

4.2.1.138

Accepted name:

(+)-caryolan-1-ol synthase

Reaction:

(+)-β-caryophyllene + H₂O = (+)-caryolan-1-ol

For diagram of humulene-based sequiterpenoid biosynthesis, click here

Glossary:

(+)-caryolan-1-ol = (1S,2R,5S,8R)-4,4,8-trimethyltricyclo[6.3.1.0^2,5]dodecan-1-ol

Other name(s):

GcoA

Systematic name:

(+)-β-caryophyllene hydrolase [cyclizing, (+)-caryolan-1-ol-forming]

Comments:

A multifunctional enzyme which also forms (+)-β-caryophyllene from farnesyl diphosphate [EC 4.2.3.89, (+)-β-caryophyllene synthase].

Links to other databases:

References:

1.	Nakano, C., Horinouchi, S. and Ohnishi, Y. Characterization of a novel sesquiterpene cyclase involved in (+)-caryolan-1-ol biosynthesis in Streptomyces griseus. J. Biol. Chem. 286 (2011) 27980–27987. [DOI] [PMID: 21693706]

[EC 4.2.1.138 created 2011 as EC 3.7.1.15, transferred 2013 to EC 4.2.1.138]

4.2.1.139

Accepted name:

pterocarpan synthase

Reaction:

a (4R)-4,2′-dihydroxyisoflavan = a pterocarpan + H₂O

For diagram of medicarpin and formononetin derivatives biosynthesis, click here

Glossary:

an isoflavan = an isoflavonoid with a 3,4-dihydro-3-aryl-2H-1-benzopyran skeleton.
(–)-medicarpin = (6aR,11aR)-9-methoxy-6a,11a-dihydro-6H-[1]benzofuro[3,2-c]chromen-3-ol
(+)-medicarpin = (6aS,11aS)-9-methoxy-6a,11a-dihydro-6H-[1]benzofuro[3,2-c]chromen-3-ol
(–)-maackiain = (6aR,12aR)-6a,12a-dihydro-6H-[1,3]dioxolo[5,6][1]benzofuro[3,2-c]chromen-3-ol
(+)-maackiain = (6aS,12aS)-6a,12a-dihydro-6H-[1,3]dioxolo[5,6][1]benzofuro[3,2-c]chromen-3-ol
(+)-pterocarpan = (6aR,11aR)-6a,11a-dihydro-6H-[1]benzofuran[3,2-c][1]benzopyran

Other name(s):

medicarpin synthase; medicarpan synthase; 7,2′-dihydroxy-4′-methoxyisoflavanol dehydratase; 2′,7-dihydroxy-4′-methoxyisoflavanol dehydratase; DMI dehydratase; DMID; 2′-hydroxyisoflavanol 4,2′-dehydratase; PTS (gene name); 4′-methoxyisoflavan-2′,4,7-triol hydro-lyase [(–)-medicarpin-forming]

Systematic name:

(4R)-4,2′-dihydroxyisoflavan hydro-lyase (pterocarpan-forming)

Comments:

The enzyme catalyses the formation of the additional ring in pterocarpan, the basic structure of phytoalexins produced by leguminous plants, including (–)-medicarpin, (+)-medicarpin, (–)-maackiain and (+)-maackiain. The enzyme requires that the hydroxyl group at C-4 of the substrate is in the (4R) configuration. The configuration of the hydrogen atom at C-3 determines whether the pterocarpan is the (+)- or (–)-enantiomer. The enzyme contains amino acid motifs characteristic of dirigent proteins.

Links to other databases:

References:

1.	Guo, L., Dixon, R.A. and Paiva, N.L. The ‘pterocarpan synthase’ of alfalfa: association and co-induction of vestitone reductase and 7,2′-dihydroxy-4′-methoxy-isoflavanol (DMI) dehydratase, the two final enzymes in medicarpin biosynthesis. FEBS Lett. 356 (1994) 221–225. [DOI] [PMID: 7805842]
2.	Guo, L., Dixon, R.A. and Paiva, N.L. Conversion of vestitone to medicarpin in alfalfa (Medicago sativa L.) is catalyzed by two independent enzymes. Identification, purification, and characterization of vestitone reductase and 7,2′-dihydroxy-4′-methoxyisoflavanol dehydratase. J. Biol. Chem. 269 (1994) 22372–22378. [PMID: 8071365]
3.	Uchida, K., Akashi, T. and Aoki, T. The missing link in leguminous pterocarpan biosynthesis is a dirigent domain-containing protein with isoflavanol dehydratase activity. Plant Cell Physiol. 58 (2017) 398–408. [PMID: 28394400]

[EC 4.2.1.139 created 2013, modified 2019]

4.2.1.140

Accepted name:

gluconate/galactonate dehydratase

Reaction:

(1) D-gluconate = 2-dehydro-3-deoxy-D-gluconate + H₂O
(2) D-galactonate = 2-dehydro-3-deoxy-D-galactonate + H₂O

For diagram of the Entner-Doudoroff pathway, click here

Other name(s):

gluconate dehydratase (ambiguous); Sso3198 (gene name); Pto0485 (gene name)

Systematic name:

D-gluconate/D-galactonate hydro-lyase

Comments:

The enzyme is involved in glucose and galactose catabolism via the nonphosphorylative variant of the Entner-Doudoroff pathway in Picrophilus torridus [3] and via the branched variant of the Entner-Doudoroff pathway in Sulfolobus solfataricus [1,2]. In vitro it utilizes D-gluconate with 6-10 fold higher catalytic efficiency than D-galactonate [1,3]. It requires Mg²⁺ for activity [1,2]. cf. EC 4.2.1.6, galactonate dehydratase, and EC 4.2.1.39, gluconate dehydratase.

Links to other databases:

References:

1.	Lamble, H.J., Milburn, C.C., Taylor, G.L., Hough, D.W. and Danson, M.J. Gluconate dehydratase from the promiscuous Entner-Doudoroff pathway in Sulfolobus solfataricus. FEBS Lett. 576 (2004) 133–136. [DOI] [PMID: 15474024]
2.	Ahmed, H., Ettema, T.J., Tjaden, B., Geerling, A.C., van der Oost, J. and Siebers, B. The semi-phosphorylative Entner-Doudoroff pathway in hyperthermophilic archaea: a re-evaluation. Biochem. J. 390 (2005) 529–540. [DOI] [PMID: 15869466]
3.	Reher, M., Fuhrer, T., Bott, M. and Schonheit, P. The nonphosphorylative Entner-Doudoroff pathway in the thermoacidophilic euryarchaeon Picrophilus torridus involves a novel 2-keto-3-deoxygluconate- specific aldolase. J. Bacteriol. 192 (2010) 964–974. [DOI] [PMID: 20023024]

[EC 4.2.1.140 created 2013]

4.2.1.141

Accepted name:

2-dehydro-3-deoxy-D-arabinonate dehydratase

Reaction:

2-dehydro-3-deoxy-D-arabinonate = 2,5-dioxopentanoate + H₂O

For diagram of D-arabinose catabolism, click here

Glossary:

2-dehydro-3-deoxy-D-arabinonate = 2-dehydro-3-deoxy-D-xylonate = 3-deoxy-L-glycero-pent-2-ulonate

Systematic name:

2-dehydro-3-deoxy-D-arabinonate hydro-lyase (2,5-dioxopentanoate-forming)

Comments:

The enzyme participates in pentose oxidation pathways that convert pentose sugars to the tricarboxylic acid cycle intermediate 2-oxoglutarate.

Links to other databases:

References:

1.	Brouns, S.J., Walther, J., Snijders, A.P., van de Werken, H.J., Willemen, H.L., Worm, P., de Vos, M.G., Andersson, A., Lundgren, M., Mazon, H.F., van den Heuvel, R.H., Nilsson, P., Salmon, L., de Vos, W.M., Wright, P.C., Bernander, R. and van der Oost, J. Identification of the missing links in prokaryotic pentose oxidation pathways: evidence for enzyme recruitment. J. Biol. Chem. 281 (2006) 27378–27388. [DOI] [PMID: 16849334]
2.	Brouns, S.J., Barends, T.R., Worm, P., Akerboom, J., Turnbull, A.P., Salmon, L. and van der Oost, J. Structural insight into substrate binding and catalysis of a novel 2-keto-3-deoxy-D-arabinonate dehydratase illustrates common mechanistic features of the FAH superfamily. J. Mol. Biol. 379 (2008) 357–371. [DOI] [PMID: 18448118]
3.	Johnsen, U., Dambeck, M., Zaiss, H., Fuhrer, T., Soppa, J., Sauer, U. and Schonheit, P. D-Xylose degradation pathway in the halophilic archaeon Haloferax volcanii. J. Biol. Chem. 284 (2009) 27290–27303. [DOI] [PMID: 19584053]

[EC 4.2.1.141 created 2013]

4.2.1.142

Accepted name:

5′-oxoaverantin cyclase

Reaction:

5′-oxoaverantin = (1′S,5′S)-averufin + H₂O

For diagram of aflatoxin biosynthesis (part 1), click here

Glossary:

5′-oxoaverantin = 1,3,6,8-tetrahydroxy-2-[(1S)-1-hydroxy-5-oxohexyl]anthracene-9,10-dione
averufin = 7,9,11-trihydroxy-2-methyl-3,4,5,6-tetrahydro-2,6-epoxy-2H-anthra[2,3-b]oxocin-8,13-dione

Other name(s):

OAVN cyclase; 5′-oxoaverantin hydro-lyase [(2′S,5′S)-averufin forming]

Systematic name:

5′-oxoaverantin hydro-lyase [(1′S,5′S)-averufin-forming]

Comments:

Isolated from the aflatoxin-producing mold Aspergillus parasiticus. The enzyme also catalyses the conversion of versiconal to versicolorin B (EC 4.2.1.143, versicolorin B synthase). Involved in aflatoxin biosynthesis.

Links to other databases:

References:

1.	Sakuno, E., Yabe, K. and Nakajima, H. Involvement of two cytosolic enzymes and a novel intermediate, 5′-oxoaverantin, in the pathway from 5′-hydroxyaverantin to averufin in aflatoxin biosynthesis. Appl. Environ. Microbiol. 69 (2003) 6418–6426. [DOI] [PMID: 14602595]
2.	Sakuno, E., Wen, Y., Hatabayashi, H., Arai, H., Aoki, C., Yabe, K. and Nakajima, H. Aspergillus parasiticus cyclase catalyzes two dehydration steps in aflatoxin biosynthesis. Appl. Environ. Microbiol. 71 (2005) 2999–3006. [DOI] [PMID: 15932995]

[EC 4.2.1.142 created 2013]

4.2.1.143

Accepted name:

versicolorin B synthase

Reaction:

versiconal = versicolorin B + H₂O

For diagram of aflatoxin biosynthesis (part 2), click here

Glossary:

versiconal = (2S,3S)-2,4,6,8-tetrahydroxy-3-(2-hydroxyethyl)anthra[2,3-b]furan-5,10-dione
versicolorin B = (3aR,12bS)-8,10,12-trihydroxy-1,2,3a,12b-tetrahydroanthra[2,3-b]furo[3,2-d]furan-6,11-dione

Other name(s):

versiconal cyclase; VBS

Systematic name:

versiconal hydro-lyase (versicolorin-B-forming)

Comments:

Isolated from the aflatoxin-producing mold Aspergillus parasiticus. Involved in aflatoxin biosynthesis.

Links to other databases:

References:

1.	Lin, B.K. and Anderson, J.A. Purification and properties of versiconal cyclase from Aspergillus parasiticus. Arch. Biochem. Biophys. 293 (1992) 67–70. [DOI] [PMID: 1731640]
2.	McGuire, S.M., Silva, J.C., Casillas, E.G. and Townsend, C.A. Purification and characterization of versicolorin B synthase from Aspergillus parasiticus. Catalysis of the stereodifferentiating cyclization in aflatoxin biosynthesis essential to DNA interaction. Biochemistry 35 (1996) 11470–11486. [DOI] [PMID: 8784203]
3.	Silva, J.C., Minto, R.E., Barry, C.E., 3rd, Holland, K.A. and Townsend, C.A. Isolation and characterization of the versicolorin B synthase gene from Aspergillus parasiticus. Expansion of the aflatoxin b1 biosynthetic gene cluster. J. Biol. Chem. 271 (1996) 13600–13608. [DOI] [PMID: 8662689]
4.	Silva, J.C. and Townsend, C.A. Heterologous expression, isolation, and characterization of versicolorin B synthase from Aspergillus parasiticus. A key enzyme in the aflatoxin B1 biosynthetic pathway. J. Biol. Chem. 272 (1997) 804–813. [DOI] [PMID: 8995367]

[EC 4.2.1.143 created 2013]

4.2.1.144

Accepted name:

3-amino-5-hydroxybenzoate synthase

Reaction:

5-amino-5-deoxy-3-dehydroshikimate = 3-amino-5-hydroxybenzoate + H₂O

Other name(s):

AHBA synthase; rifK (gene name)

Systematic name:

5-amino-5-deoxy-3-dehydroshikimate hydro-lyase (3-amino-5-hydroxybenzoate-forming)

Comments:

A pyridoxal 5′-phosphate enzyme. The enzyme from the bacterium Amycolatopsis mediterranei participates in the pathway for rifamycin B biosynthesis. The enzyme also functions as a transaminase earlier in the pathway, producing UDP-α-D-kanosamine [3].

Links to other databases:

References:

1.	Kim, C.G., Yu, T.W., Fryhle, C.B., Handa, S. and Floss, H.G. 3-Amino-5-hydroxybenzoic acid synthase, the terminal enzyme in the formation of the precursor of mC₇N units in rifamycin and related antibiotics. J. Biol. Chem. 273 (1998) 6030–6040. [DOI] [PMID: 9497318]
2.	Eads, J.C., Beeby, M., Scapin, G., Yu, T.W. and Floss, H.G. Crystal structure of 3-amino-5-hydroxybenzoic acid (AHBA) synthase. Biochemistry 38 (1999) 9840–9849. [DOI] [PMID: 10433690]
3.	Floss, H.G., Yu, T.W. and Arakawa, K. The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC₇N units in ansamycin and mitomycin antibiotics: a review. J. Antibiot. (Tokyo) 64 (2011) 35–44. [DOI] [PMID: 21081954]

[EC 4.2.1.144 created 2013]

4.2.3.143

Accepted name:

kunzeaol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = kunzeaol + diphosphate

For diagram of germacrene sesquiterpenoid biosynthesis, click here

Glossary:

kunzeaol = 6β-hydroxygermacra-1(10),4-diene = (1R,2E,6E,10R)-3,7-dimethyl-10-isopropylcyclodeca-2,6-dienol

Other name(s):

TgTPS2 (gene name)

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (kunzeaol-forming)

Comments:

Isolated from the root of the plant Thapsia garganica. The enzyme also produces germacrene D, bicyclogermacrene and traces of other sesquiterpenoids. See EC 4.2.3.77, (+)-germacrene D synthase and EC 4.2.3.100, bicyclogermacrene synthase.

Links to other databases:

References:

1.	Pickel, B., Drew, D.P., Manczak, T., Weitzel, C., Simonsen, H.T. and Ro, D.K. Identification and characterization of a kunzeaol synthase from Thapsia garganica: implications for the biosynthesis of the pharmaceutical thapsigargin. Biochem. J. 448 (2012) 261–271. [DOI] [PMID: 22938155]

[EC 4.2.3.143 created 2013]

4.2.99.22

Accepted name:

tuliposide A-converting enzyme

Reaction:

6-tuliposide A = tulipalin A + D-glucose

Glossary:

6-tuliposide A = 6-O-(4-hydroxy-2-methylenebutanoyl)-D-glucose
tulipalin A = 2-methylenebutanolactone

Other name(s):

tuliposide-converting enzyme; 6-O-(4′-hydroxy-2′-methylenebutyryl)-D-glucose acyltransferase (lactone-forming); TCA; TCEA

Systematic name:

6-tuliposide A D-glucose-lyase (tulipalin-A-forming)

Comments:

Isolated from the plant Tulipa gesneriana (tulip). The reaction is an intramolecular transesterification producing the lactone. The enzyme also has a weak activity with 6-tuliposide B and 6-O-benzoyl-D-glucose.

Links to other databases:

References:

1.	Kato, Y., Shoji, K., Ubukata, M., Shigetomi, K., Sato, Y., Nakajima, N. and Ogita, S. Purification and characterization of a tuliposide-converting enzyme from bulbs of Tulipa gesneriana. Biosci. Biotechnol. Biochem. 73 (2009) 1895–1897. [DOI] [PMID: 19661715]
2.	Nomura, T., Ogita, S. and Kato, Y. A novel lactone-forming carboxylesterase: molecular identification of a tuliposide A-converting enzyme in tulip. Plant Physiol. 159 (2012) 565–578. [DOI] [PMID: 22474185]

[EC 4.2.99.22 created 2013]

4.3.1.26

Transferred entry:

chromopyrrolate synthase. Now EC 1.21.3.9, dichlorochromopyrrolate synthase

[EC 4.3.1.26 created 2010, deleted 2013]

6.3.2.40

Accepted name:

cyclopeptine synthase

Reaction:

2 ATP + S-adenosyl-L-methionine + anthranilate + L-phenylalanine = cyclopeptine + 2 AMP + 2 diphosphate + S-adenosyl-L-homocysteine

For diagram of cyclopeptine, cyclopenine and viridicatin biosynthesis, click here

Glossary:

cyclopeptine = (3S)-3-benzyl-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione
4′-methoxycyclopeptine = (3S)-3-(4-methoxybenzyl)-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

Systematic name:

S-adenosyl-L-methionine:anthranilate:L-phenylalanine ligase (cyclopeptine-forming)

Comments:

Cyclopeptine synthase is the key enzyme of benzodiazepine alkaloid biosynthesis in several fungi species. The enzyme is a non-ribosomal peptide synthase. It is also active with O-methyl-L-tyrosine forming 4′-methoxycyclopeptine.

Links to other databases:

References:

1.	Lerbs, W. and Luckner, M. Cyclopeptine synthetase activity in surface cultures of Penicillium cyclopium. J. Basic Microbiol. 25 (1985) 387–391. [DOI] [PMID: 2995633]
2.	Gerlach, M, Schwelle, N., Lerbs, W. and Luckner, M. Enzymatic synthesis of cyclopeptine intermediates in Penicillium cyclopium. Phytochemistry 24 (1985) 1935–1939.
3.	Ishikawa, N., Tanaka, H., Koyama, F., Noguchi, H., Wang, C.C., Hotta, K. and Watanabe, K. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew. Chem. Int. Ed. Engl. 53 (2014) 12880–12884. [DOI] [PMID: 25251934]

[EC 6.3.2.40 created 2013]

6.3.4.1

Transferred entry:

GMP synthase. Now included in EC 6.3.5.2, GMP synthase (glutamine-hydrolysing)

[EC 6.3.4.1 created 1961, deleted 2013]

*EC

6.3.4.2

Accepted name:

CTP synthase (glutamine hydrolysing)

Reaction:

ATP + UTP + L-glutamine = ADP + phosphate + CTP + L-glutamate (overall reaction)
(1a) L-glutamine + H₂O = L-glutamate + NH₃
(1b) ATP + UTP + NH₃ = ADP + phosphate + CTP

Other name(s):

UTP—ammonia ligase; cytidine triphosphate synthetase; uridine triphosphate aminase; cytidine 5′-triphosphate synthetase; CTPS (gene name); pyrG (gene name); CTP synthase; UTP:ammonia ligase (ADP-forming)

Systematic name:

UTP:L-glutamine amido-ligase (ADP-forming)

Comments:

The enzyme contains three functionally distinct sites: an allosteric GTP-binding site, a glutaminase site where glutamine hydrolysis occurs (cf. EC 3.5.1.2, glutaminase), and the active site where CTP synthesis takes place. The reaction proceeds via phosphorylation of UTP by ATP to give an activated intermediate 4-phosphoryl UTP and ADP [4,5]. Ammonia then reacts with this intermediate generating CTP and a phosphate. The enzyme can also use ammonia from the surrounding solution [3,6].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9023-56-7

References:

1.	Lieberman, I. Enzymatic amination of uridine triphosphate to cytidine triphosphate. J. Biol. Chem. 222 (1956) 765–775. [PMID: 13367044]
2.	Long, C.W., Levitzki, A., Houston, L.L and Koshland, D.E., Jr. Subunit structures and interactions of CTP synthetase. Fed. Proc. 28 (1969) 342.
3.	Levitzki, A. and Koshland, D.E., Jr. Ligand-induced dimer-to-tetramer transformation in cytosine triphosphate synthetase. Biochemistry 11 (1972) 247–253. [PMID: 4550560]
4.	von der Saal, W., Anderson, P.M. and Villafranca, J.J. Mechanistic investigations of Escherichia coli cytidine-5′-triphosphate synthetase. Detection of an intermediate by positional isotope exchange experiments. J. Biol. Chem. 260 (1985) 14993–14997. [PMID: 2933396]
5.	Lewis, D.A. and Villafranca, J.J. Investigation of the mechanism of CTP synthetase using rapid quench and isotope partitioning methods. Biochemistry 28 (1989) 8454–8459. [PMID: 2532543]
6.	Wadskov-Hansen, S.L., Willemoes, M., Martinussen, J., Hammer, K., Neuhard, J. and Larsen, S. Cloning and verification of the Lactococcus lactis pyrG gene and characterization of the gene product, CTP synthase. J. Biol. Chem. 276 (2001) 38002–38009. [DOI] [PMID: 11500486]

[EC 6.3.4.2 created 1961, modified 2013]

6.3.4.21

Accepted name:

nicotinate phosphoribosyltransferase

Reaction:

nicotinate + 5-phospho-α-D-ribose 1-diphosphate + ATP + H₂O = β-nicotinate D-ribonucleotide + diphosphate + ADP + phosphate

For diagram of NAD⁺ biosynthesis, click here

Other name(s):

niacin ribonucleotidase; nicotinic acid mononucleotide glycohydrolase; nicotinic acid mononucleotide pyrophosphorylase; nicotinic acid phosphoribosyltransferase; nicotinate-nucleotide:diphosphate phospho-α-D-ribosyltransferase

Systematic name:

5-phospho-α-D-ribose 1-diphosphate:nicotinate ligase (ADP, diphosphate-forming)

Comments:

The enzyme, which is involved in pyridine nucleotide recycling, can form β-nicotinate D-ribonucleotide and diphosphate from nicotinate and 5-phospho-α-D-ribose 1-diphosphate (PRPP) in the absence of ATP. However, when ATP is available the enzyme is phosphorylated resulting in a much lower K_m for nicotinate. The phospho-enzyme is hydrolysed during the transferase reaction, regenerating the low affinity form. The presence of ATP shifts the products/substrates equilibrium from 0.67 to 1100 [4].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9030-26-6

References:

1.	Imsande, J. Pathway of diphosphopyridine nucleotide biosynthesis in Escherichia coli. J. Biol. Chem. 236 (1961) 1494–1497. [PMID: 13717628]
2.	Imsande, J. and Handler, P. Biosynthesis of diphosphopyridine nucleotide. III. Nicotinic acid mononucleotide pyrophosphorylase. J. Biol. Chem. 236 (1961) 525–530. [PMID: 13717627]
3.	Kosaka, A., Spivey, H.O. and Gholson, R.K. Nicotinate phosphoribosyltransferase of yeast. Purification and properties. J. Biol. Chem. 246 (1971) 3277–3283. [PMID: 4324895]
4.	Vinitsky, A. and Grubmeyer, C. A new paradigm for biochemical energy coupling. Salmonella typhimurium nicotinate phosphoribosyltransferase. J. Biol. Chem. 268 (1993) 26004–26010. [PMID: 7503993]

[EC 6.3.4.21 created 1961 as EC 2.4.2.11, transferred 2013 to EC 6.3.4.21]

6.3.4.22

Accepted name:

tRNA^Ile²-agmatinylcytidine synthase

Reaction:

ATP + agmatine + [tRNA^Ile²]-cytidine³⁴ + H₂O = [tRNA^Ile²]-2-agmatinylcytidine³⁴ + AMP + 2 phosphate

Other name(s):

TiaS; AF2259; tRNA^Ile-2-agmatinylcytidine synthetase; tRNA^Ile-agm²C synthetase; tRNA^Ile-agmatidine synthetase

Systematic name:

agmatine:[tRNA^Ile]-cytidine³⁴ ligase

Comments:

The enzyme from the archaeon Archaeoglobus fulgidus modifies the wobble base of the CAU anticodon of the archaeal tRNA^Ile² at the oxo group in position 2 of cytidine³⁴. This modification is crucial for accurate decoding of the genetic code. In bacteria EC 6.3.4.19, tRNA^Ile-lysidine synthase, catalyses the modification of [tRNA^Ile²]-cytidine³⁴ to [tRNA^Ile²]-lysidine³⁴ .

Links to other databases: