An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: L-galactose 1-dehydrogenase (NAD+)
Reaction: L-galactose + NAD+ = L-galactono-1,4-lactone + NADH + H+ (overall reaction)
(1a) L-galactose + NAD+ = L-galactono-1,5-lactone + NADH + H+
(1b) L-galactono-1,5-lactone = L-galactono-1,4-lactone (spontaneous)
Other name(s): L-GalDH; L-galactose dehydrogenase; L-galactose 1-dehydrogenase
Systematic name: L-galactose:NAD+ 1-oxidoreductase
Comments: The enzyme catalyses a step in the ascorbate biosynthesis in higher plants (Smirnoff-Wheeler pathway). The activity with NADP+ is less than 10% of the activity with NAD+. cf. EC 1.1.1.445, L-galactose 1-dehydrogenase (NADP+).
Links to other databases: BRENDA, EXPASY, GENE, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Mieda, T., Yabuta, Y., Rapolu, M., Motoki, T., Takeda, T., Yoshimura, K., Ishikawa, T. and Shigeoka, S. Feedback inhibition of spinach L-galactose dehydrogenase by L-ascorbate. Plant Cell Physiol. 45 (2004) 1271-1279. [PMID: 15509850]
2. Gatzek, S., Wheeler, G.L. and Smirnoff, N. Antisense suppression of L-galactose dehydrogenase in Arabidopsis thaliana provides evidence for its role in ascorbate synthesis and reveals light modulated L-galactose synthesis. Plant J. 30 (2002) 541-553. [PMID: 12047629]
3. Wheeler, G.L., Jones, M.A. and Smirnoff, N. The biosynthetic pathway of vitamin C in higher plants. Nature 393 (1998) 365-369. [PMID: 9620799]
4. Oh, M.M., Carey, E.E. and Rajashekar, C.B. Environmental stresses induce health-promoting phytochemicals in lettuce. Plant Physiol. Biochem. 47 (2009) 578-583. [PMID: 19297184]
Accepted name: L-galactose 1-dehydrogenase (NADP+)
Reaction: L-galactose + NADP+ = L-galactono-1,5-lactone + NADPH + H+
Other name(s): lgaA (gene name); Bvu0219
Systematic name: L-galactose:NADP+ 1-oxidoreductase
Comments: The enzyme, characterized from the bacterium Phocaeicola vulgatus, catalyses a step in an L-galactose utilization metabolic pathway. The product, L-galactono-1,5-lactone, can be spontaneously converted to the more stable L-galactono-1,4-lactone, but the subsequent metabolic enzyme (EC 3.1.1.126) specifically hydrolyses L-galactono-1,5-lactone. cf. EC 1.1.1.316 L-galactose 1-dehydrogenase (NAD+).
References:
1. Hobbs, M.E., Williams, H.J., Hillerich, B., Almo, S.C. and Raushel, F.M. L-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota. Biochemistry 53 (2014) 4661-4670. [PMID: 24963813]
Accepted name: L-cysteinolate dehydrogenase
Reaction: L-cysteinolate + 2 NAD+ + H2O = L-cysteate + 2 NADH + 3 H+ (overall reaction)
(1a) L-cysteinolate + NAD+ = L-cysteinal + NADH + H+
(1b) L-cysteinal + NAD+ + H2O = L-cysteate + NADH + 2 H+
Glossary: cysteinolate = 2-amino-3-hydroxypropane-1-sulfonate
L-cysteinolate = (2R)-2-amino-3-hydroxypropane-1-sulfonate
Other name(s): claB (gene name); hpsN (gene name); L-cysteinolic acid dehydrogenase
Systematic name: L-cysteinolate:NAD+ oxidoreductase
Comments: Contains Zn2+. The enzyme, characterized from the bacteria Ruegeria pomeroyi and Bilophila sp. 4_1_30, participates in a D-cysteinolate degradation pathway. The enzyme, which is specific for NAD+ as a cosubstrate, has no activity with D-cysteinolate.
References:
1. Burchill, L., Stewart, A.WE., Pallasdies, L., Lee, M., Coe, L.SY., Zudich, L., Jebeli, L., Sharma, M., Hofferek, V., McConville, M.J., Davies, G.J., Scott, N.E., Durham, B.P. and Williams, S.J. Bridging a gap in marine sulfur cycling: discovery of a D-cysteinolic acid degradation pathway. J. Am. Chem. Soc. 147 (2025) 47934-47941. [PMID: 41404639]
2. Liu, X., Hu, Y., An, J., Zhang, C., Tan, J., Wei, Y. and Zhang, Y. A pathway for D-cysteinolate degradation in sulfate- and sulfite-reducing bacteria. J. Biol. Chem. 302 (2026) 111055. [PMID: 41391761]
Accepted name: L-lactate dehydrogenase (quinone)
Reaction: L-lactate + a quinone = pyruvate + a quinol
Other name(s): lldD; lctD (gene name)
Systematic name: L-lactate:quinone 2-oxidoreductase
Comments: The enzyme is associated with the membrane and transfers electrons from lactate directly to the membrane quinone pool. In the bacterium Escherichia coli the enzyme contains FMN.
References:
1. Futai, M. and Kimura, H. Inducible membrane-bound L-lactate dehydrogenase from Escherichia coli. Purification and properties. J. Biol. Chem. 252 (1977) 5820-5827. [PMID: 18473]
2. Dong, J.M., Taylor, J.S., Latour, D.J., Iuchi, S. and Lin, E.C. Three overlapping lct genes involved in L-lactate utilization by Escherichia coli. J. Bacteriol. 175 (1993) 6671-6678. [PMID: 8407843]
3. Iuchi, S., Aristarkhov, A., Dong, J.M., Taylor, J.S. and Lin, E.C. Effects of nitrate respiration on expression of the Arc-controlled operons encoding succinate dehydrogenase and flavin-linked L-lactate dehydrogenase. J. Bacteriol. 176 (1994) 1695-1701. [PMID: 8132465]
4. Stansen, C., Uy, D., Delaunay, S., Eggeling, L., Goergen, J.L. and Wendisch, V.F. Characterization of a Corynebacterium glutamicum lactate utilization operon induced during temperature-triggered glutamate production. Appl. Environ. Microbiol. 71 (2005) 5920-5928. [PMID: 16204505]
5. Billig, S., Schneefeld, M., Huber, C., Grassl, G.A., Eisenreich, W. and Bange, F.C. Lactate oxidation facilitates growth of Mycobacterium tuberculosis in human macrophages. Sci. Rep. 7 (2017) 6484. [PMID: 28744015]
6. Stanley, S., Wang, X., Liu, Q., Kwon, Y.Y., Frey, A.M., Hicks, N.D., Vickers, A.J., Hui, S. and Fortune, S.M. Ongoing evolution of the Mycobacterium tuberculosis lactate dehydrogenase reveals the pleiotropic effects of bacterial adaption to host pressure. PLoS Pathog. 20 (2024) e1012050. [PMID: 38422159]
Accepted name: aldehyde dehydrogenase (FAD-independent)
Reaction: an aldehyde + H2O + flavodoxin = a carboxylate + reduced flavodoxin
Other name(s): aldehyde oxidase; aldehyde oxidoreductase; Mop; AORDd
Systematic name: aldehyde:flavodoxin oxidoreductase (FAD-independent)
Comments: The enzyme, best characterized from the sulfate-reducing bacterium Megalodesulfovibrio gigas, belongs to the xanthine oxidase family of enzymes. However, it lacks the FAD-binding domain typically found in members of this family. Instead, it transfers electrons to flavodoxin, which fulfills the role of the missing domain. The enzyme contains a molybdenum-molybdopterin-cytosine dinucleotide (MCD) cofactor and two types of [2Fe-2S] clusters per monomer.
References:
1. Romao, M.J., Barata, B.A., Archer, M., Lobeck, K., Moura, I., Carrondo, M.A., LeGall, J., Lottspeich, F., Huber, R. and Moura, J.J. Subunit composition, crystallization and preliminary crystallographic studies of the Desulfovibrio gigas aldehyde oxidoreductase containing molybdenum and [2Fe-2S] centers. Eur. J. Biochem. 215 (1993) 729-732. [PMID: 8354279]
2. Barata, B.A., LeGall, J. and Moura, J.J. Aldehyde oxidoreductase activity in Desulfovibrio gigas: in vitro reconstitution of an electron-transfer chain from aldehydes to the production of molecular hydrogen. Biochemistry 32 (1993) 11559-11568. [PMID: 8218223]
3. Romao, M.J., Archer, M., Moura, I., Moura, J.J., LeGall, J., Engh, R., Schneider, M., Hof, P. and Huber, R. Crystal structure of the xanthine oxidase-related aldehyde oxido-reductase from D. gigas. Science 270 (1995) 1170-1176. [PMID: 7502041]
4. Duarte, R.O., Archer, M., Dias, J.M., Bursakov, S., Huber, R., Moura, I., Romao, M.J. and Moura, J.J. Biochemical/spectroscopic characterization and preliminary X-ray analysis of a new aldehyde oxidoreductase isolated from Desulfovibrio desulfuricans ATCC 27774. Biochem. Biophys. Res. Commun. 268 (2000) 745-749. [PMID: 10679276]
5. Andrade, S.L., Brondino, C.D., Feio, M.J., Moura, I. and Moura, J.J. Aldehyde oxidoreductase activity in Desulfovibrio alaskensis NCIMB 13491. EPR assignment of the proximal [2Fe-2S] cluster to the Mo site. Eur. J. Biochem. 267 (2000) 2054-2061. [PMID: 10727945]
6. Rebelo, J.M., Dias, J.M., Huber, R., Moura, J.J. and Romao, M.J. Structure refinement of the aldehyde oxidoreductase from Desulfovibrio gigas (MOP) at 1.28 Å. J. Biol. Inorg. Chem. 6 (2001) 791-800. [PMID: 11713686]
7. Uchida, H., Kondo, D., Yamashita, A., Nagaosa, Y., Sakurai, T., Fujii, Y., Fujishiro, K., Aisaka, K. and Uwajima, T. Purification and characterization of an aldehyde oxidase from Pseudomonas sp. KY 4690. FEMS Microbiol. Lett. 229 (2003) 31-36. [PMID: 14659539]
8. Krippahl, L., Palma, P.N., Moura, I. and Moura, J.JG. Modelling the electron-transfer complex between aldehyde oxidoreductase and flavodoxin. Eur J. Inorg. Chem. 2006 (2006) 3835-3840.
[EC 1.2.99.7 Transferred entry: aldehyde dehydrogenase (FAD-independent). Now classified as EC 1.2.8.2, aldehyde dehydrogenase (FAD-independent). (EC 1.2.99.7 created 2004, deleted 2025)]
Accepted name: 2-hydroxy-3-oxopropanoyl-[acyl-carrier-protein] 3-hydroxylase
Reaction: (2R)-2-hydroxy-3-oxopropanoyl-[acyl-carrier-protein] + H2O + acceptor = a (2R)-2-hydroxymalonyl-[acyl-carrier-protein] + reduced acceptor
Other name(s): fkbI (gene name); asm15 (gene name); zmaE (gene name)
Systematic name: a (2R)-2-hydroxy-3-oxopropanoyl-[acp]:acceptor oxidoreductase (3-hydroxylating)
Comments: Contains an FAD cofactor. The enzyme participates in the biosynthesis of 2-hydroxymalonate and 2-methoxymalonate, unusual polyketide synthase extender units used in the biosynthesis of some polyketide products, such as ascomycin (FK520), tacrolimus (FK506) and the ansamitocins.
References:
1. Wu, K., Chung, L., Revill, W.P., Katz, L. and Reeves, C.D. The FK520 gene cluster of Streptomyces hygroscopicus var. ascomyceticus (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender units. Gene 251 (2000) 81-90. [PMID: 10863099]
2. Kato, Y., Bai, L., Xue, Q., Revill, W.P., Yu, T.W. and Floss, H.G. Functional expression of genes involved in the biosynthesis of the novel polyketide chain extension unit, methoxymalonyl-acyl carrier protein, and engineered biosynthesis of 2-desmethyl-2-methoxy-6-deoxyerythronolide B. J. Am. Chem. Soc. 124 (2002) 5268-5269. [PMID: 11996558]
3. Watanabe, K., Khosla, C., Stroud, R.M. and Tsai, S.C. Crystal structure of an Acyl-ACP dehydrogenase from the FK520 polyketide biosynthetic pathway: insights into extender unit biosynthesis. J. Mol. Biol. 334 (2003) 435-444. [PMID: 14623185]
4. Chan, Y.A., Boyne, M.T., 2nd, Podevels, A.M., Klimowicz, A.K., Handelsman, J., Kelleher, N.L. and Thomas, M.G. Hydroxymalonyl-acyl carrier protein (ACP) and aminomalonyl-ACP are two additional type I polyketide synthase extender units. Proc. Natl. Acad. Sci. USA 103 (2006) 14349-14354. [PMID: 16983083]
Accepted name: 2-coumarate reductase
Reaction: 3-(2-hydroxyphenyl)propanoate + NAD+ = 2-coumarate + NADH + H+
Other name(s): melilotate dehydrogenase
Systematic name: 3-(2-hydroxyphenyl)propanoate:NAD+ oxidoreductase
Comments: The enzyme, isolated from an Arthrobacter species, is highly specific for 2-coumarate. cf. EC 1.3.1.130, hydroxycinnamate reductase.
Links to other databases: BRENDA, EXPASY, GENE, KEGG, MetaCyc, CAS registry number: 37251-10-8
References:
1. Levy, C. C. Metabolism of coumarin by a micro-organism: o-coumaric acid as an intermediate between coumarin and melilotic acid. Nature 204 (1964) 1059-1061. [PMID: 14243380]
2. Levy, C.C. and Weinstein, G.D. The metabolism of coumarin by a microorganism. II. The reduction of o-coumaric acid to melilotic acid. Biochemistry 3 (1964) 1944-1947. [PMID: 14269315]
Accepted name: hydroxycinnamate reductase
Reaction: a hydroxy-dihydrocinnamate + NAD+ = a hydroxy-trans-cinnamate + NADH + H+
Other name(s): hcrA (gene name); hcrB (gene name); hcrF (gene name); par1 (gene name); crdA (gene name); crdB (gene name)
Systematic name: hydroxycinnamate:NAD+ oxidoreductase (hydroxy-trans-cinnamate-forming)
Comments: Requires FMN. The enzyme, characterized from assorted lactic acid bacteria and the anaerobic bacterium Vibrio ruber, acts on multiple hydroxy-trans-cinnamic acids including 2-coumarate, 3-coumarate, 4-coumarate, ferulate, caffeate and sinapate. It participates in an alternative degradation pathway of hydroxycinnamic acids. The main pathway involves EC 4.1.1.102, phenacrylate decarboxylase, and EC 1.3.1.131, vinylphenol reductase. cf. EC 1.3.1.11, 2-coumarate reductase.
References:
1. Santamaria, L., Reveron, I., Lopez de Felipe, F., de Las Rivas, B. and Munoz, R. Unravelling the reduction pathway as an alternative metabolic route to hydroxycinnamate decarboxylation in Lactobacillus plantarum. Appl. Environ. Microbiol. 84 (2018) e01123-18. [PMID: 29776925]
2. Gaur, G., Oh, J.H., Filannino, P., Gobbetti, M., van Pijkeren, J.P. and Ganzle, M.G. Genetic determinants of hydroxycinnamic acid metabolism in heterofermentative lactobacilli. Appl. Environ. Microbiol. 86 (2020) e02461-19. [PMID: 31862715]
3. Gaur, G. and Ganzle, M. Biochemical characterization of HcrF from Limosilactobacillus fermentum, a NADH-dependent 2-ene reductase with activity on hydroxycinnamic acids. Lett. Appl. Microbiol. 77 (2024) ovae109. [PMID: 39521943]
4. Bertsova, Y.V., Serebryakova, M.V., Anashkin, V.A., Baykov, A.A. and Bogachev, A.V. A Redox-Regulated, Heterodimeric NADH:cinnamate Reductase in Vibrio ruber. Biochemistry (Mosc.) 89 (2024) 241-256. [PMID: 38622093]
Accepted name: vinylphenol reductase
Reaction: (1) 4-ethylphenol + NAD+ = 4-vinylphenol + NADH + H+
(2) 4-ethylcatechol + NAD+ = 4-vinylcatechol + NADH + H+
(3) 4-ethylguaiacol + NAD+ = 4-vinylguaiacol + NADH + H+
Other Names: vprA (gene name)
Systematic name: 4-ethylphenol:NAD+ 7-oxidoreductase
Comments: Requires FAD. The enzyme, characterized from the lactic acid bacterium Lactiplantibacillus plantarum and the yeast Brettanomyces bruxellensis, is involved in the production of ethylphenols during the degradation of hydroxycinnamic acids.
References:
1. Tchobanov, I., Gal, L., Guilloux-Benatier, M., Remize, F., Nardi, T., Guzzo, J., Serpaggi, V. and Alexandre, H. Partial vinylphenol reductase purification and characterization from Brettanomyces bruxellensis. FEMS Microbiol. Lett. 284 (2008) 213-217. [PMID: 18576949]
2. Granato, T.M., Romano, D., Vigentini, I., Foschino, R.C., Monti, D., Mamone, G., Ferranti, P., Nitride, C., Iametti, S., Bonomi, F. and Molinari, F. New insights on the features of the vinyl phenol reductase from the wine-spoilage yeast Dekkera/Brettanomyces bruxellensis. Ann Microbiol 65 (2015) 321-329.
3. Romano, D., Valdetara, F., Zambelli, P., Galafassi, S., De Vitis, V., Molinari, F., Compagno, C., Foschino, R. and Vigentini, I. Cloning the putative gene of vinyl phenol reductase of Dekkera bruxellensis in Saccharomyces cerevisiae. Food Microbiol 63 (2017) 92-100. [PMID: 28040186]
4. Santamaria, L., Reveron, I., Lopez de Felipe, F., de Las Rivas, B. and Munoz, R. Unravelling the reduction pathway as an alternative metabolic route to hydroxycinnamate decarboxylation in Lactobacillus plantarum. Appl. Environ. Microbiol. 84 (2018) e01123-18. [PMID: 29776925]
Accepted name: N-acyl-aromatic-amino-acid desaturase
Reaction: (1) an N-acyl-L-tryptophan + O2 = a (2E)-N-acyl-2-dehydrotryptophan + H2O2
(2) an N-acyl-L-tyrosine + O2 = a (2E)-N-acyl-2-dehydrotyrosine + H2O2
(3) an N-acyl-L-phenylalanine + O2 = a (2E)-N-acyl-2-dehydrophenylalanine + H2O2
Other name(s): tyzC (gene name); oxzB (gene name); trzS (gene name)
Systematic name: N-acyl-aromatic amino acid:oxygen 2-oxidoreductase
Comments: Contains FMN. The enzyme catalyses a step in the biosynthesis of oxazolone compounds (phenazolones, tyrazolones, and tryptazolones), which have been reported from Gram-negative as well as Gram-positive bacteria. The enzyme acts along EC 6.1.3.2, N-acyl-2-dehydroaromatic-amino-acid cyclase, and the order in which the two enzymes act has not been determined conclusively. In some organisms the two enzymes form a fusion protein.
References:
1. de Rond, T., Asay, J.E. and Moore, B.S. Co-occurrence of enzyme domains guides the discovery of an oxazolone synthetase. Nat. Chem. Biol. 17 (2021) 794-799. [PMID: 34099916]
2. Grigg, J.C., Copp, J.N., Krekhno, J.MC., Liu, J., Ibrahimova, A. and Eltis, L.D. Deciphering the biosynthesis of a novel lipid in Mycobacterium tuberculosis expands the known roles of the nitroreductase superfamily. J. Biol. Chem. 299 (2023) 104924. [PMID: 37328106]
3. Kleetz, J., Grigg, J.C., Hassan, A.A., Ibtisam, A., Copp, J.N., Lian, J., Liu, J. and Eltis, L.D. The biosynthesis of N-acylated tryptazolone in Mycobacterium tuberculosis and related bacteria. J. Biol. Chem. 302 (2026) 111079. [PMID: 41429352]
Accepted name: pseudopaline dehydrogenase
Reaction: pseudopaline + H2O + NAD(P)+ = N-[(3S)-3-amino-3-carboxypropyl]-L-histidine + 2-oxoglutarate + NAD(P)H + H+
Glossary: pseudopaline = (2R)-2-{[(1S)-1-carboxylato-3-{[(1S)-1-carboxylato-2-(1H-imidazol-4-yl)ethyl]amino}propyl]amino}pentanedioate
Other name(s): pseudopaline synthase; cntM (gene name) (ambiguous)
Systematic name: pseudopaline:NADP+ oxidoreductase [N-[(3S)-3-amino-3-carboxypropyl]-L-histidine]-forming
Comments: The enzyme, characterized from the bacterium Pseudomonas aeruginosa, catalyses the last reaction in the biosynthesis of the metallophore pseudopaline, which is involved in the acquisition of nickel, copper, cobalt, and zinc. The catalytic efficiency with NADPH is 2-fold higher than with NADH. cf. EC 1.5.1.52, staphylopine dehydrogenase.
References:
1. McFarlane, J.S. and Lamb, A.L. Biosynthesis of an opine metallophore by Pseudomonas aeruginosa. Biochemistry 56 (2017) 5967-5971. [PMID: 29091735]
2. McFarlane, J.S., Davis, C.L. and Lamb, A.L. Staphylopine, pseudopaline, and yersinopine dehydrogenases: A structural and kinetic analysis of a new functional class of opine dehydrogenase. J. Biol. Chem. 293 (2018) 8009-8019. [PMID: 29618515]
3. Bosc, L., Secher, T., Ball, G., Le Pennec, D., Tribout, M., Ba, M., Bai, Y., Ouerdane, L., Arnoux, P., Denis, Y., Lei, X., Bordi, C., Heuze-Vourc'h, N., Haussler, S., Gomez, N.O. and Voulhoux, R. Pseudopaline-mediated zinc uptake by Pseudomonas aeruginosa drives clinically relevant phenotypes and infection outcomes. Infect. Immun. 94 (2026) e0045325. [PMID: 41532760]
Accepted name: pyruvic oxime dioxygenase
Reaction: pyruvate oxime + O2 = pyruvate + nitrite
Glossary: pyruvate oxime = pyruvic oxime = 2-(hydroxyimino)propanoate
Other name(s): POD (ambiguous)
Systematic name: pyruvate oxime:oxygen oxidoreductase (nitrite-forming)
Comments: This enzyme, first reported from the heterotrophic nitrifier Alcaligenes faecalis, oxidizes pyruvate oxime, which is formed spontaneously from hydroxylamine and pyruvate, to nitrite and pyruvate. Despite its similarity to class II aldolases, the active site contains Fe(II) rather than the common Zn(II). Activity requires that the iron is kept in Fe(II) state, and is enhanced by inclusion of reducing agents in the reaction mixture. The iron at the active site is coordinated by three histidines and three water molecules.
References:
1. Ono, Y., Makino, N., Hoshino, Y., Shoji, K. and Yamanaka, T. An iron dioxygenase from Alcaligenes faecalis catalyzing the oxidation of pyruvic oxime to nitrite. FEMS Microbiol. Lett. 139 (1996) 103-108. [PMID: 8674977]
2. Ono, Y., Enokiya, A., Masuko, D., Shoji, K. and Yamanaka, T. Pyruvic oxime dioxygenase from the heterotrophic nitrifier Alcaligenes faecalis: purification, and molecular and enzymatic properties. Plant Cell Physiol. 40 (1999) 47-52.
3. Tsujino, S., Uematsu, C., Dohra, H. and Fujiwara, T. Pyruvic oxime dioxygenase from heterotrophic nitrifier Alcaligenes faecalis is a nonheme Fe(II)-dependent enzyme homologous to class II aldolase. Sci. Rep. 7 (2017) 39991. [PMID: 28059164]
4. Tsujino, S., Yamada, Y., Senda, M., Nakamura, A., Senda, T. and Fujiwara, T. Structural characterization of pyruvic oxime dioxygenase, a key enzyme in heterotrophic nitrification. J. Bacteriol. 207 (2025) e0034224. [PMID: 39772954]
Accepted name: thymine dioxygenase
Reaction: thymine + 3 2-oxoglutarate + 3 O2 = uracil-5-carboxylate + 3 succinate + 3 CO2 + H2O (overall reaction)
(1a) thymine + 2-oxoglutarate + O2 = 5-hydroxymethyluracil + succinate + CO2
(1b) 5-hydroxymethyluracil + 2-oxoglutarate + O2 = 5-formyluracil + succinate + CO2 + H2O
(1c) 5-formyluracil + 2-oxoglutarate + O2 = uracil-5-carboxylate + succinate + CO2
Other name(s): thymine 7-hydroxylase; 5-hydroxy-methyluracil dioxygenase; 5-hydroxymethyluracil oxygenase
Systematic name: thymine,2-oxoglutarate:oxygen oxidoreductase (7-hydroxylating)
Comments: Requires Fe2+ and ascorbate. The enzyme, found in fungi, catalyses the oxidation of thymine to uracil 5-carboxylate as part of a thymidine salvage pathway.
Links to other databases: BRENDA, EXPASY, GENE, KEGG, MetaCyc, PDB, CAS registry number: 37256-67-0
References:
1. Bankel, L., Holme, E., Lindstedt, G. and Lindstedt, S. Oxygenases involved in thymine and thymidine metabolism in Neurospora crassa. FEBS Lett. 21 (1972) 135-138. [PMID: 11946494]
2. Liu, C.-K., Hsu, C.-A. and Abbott, M.T. Catalysis of three sequential dioxygenase reactions by thymine 7-hydroxylase. Arch. Biochem. Biophys. 159 (1973) 180-187. [PMID: 4274083]
3. Warn-Cramer, B.J., Macrander, L.A. and Abbott, M.T. Markedly different ascorbate dependencies of the sequential α-ketoglutarate dioxygenase reactions catalyzed by an essentially homogeneous thymine 7-hydroxylase from Rhodotorula glutinis. J. Biol. Chem. 258 (1983) 10551-10557. [PMID: 6684117]
4. Smiley, J.A., Kundracik, M., Landfried, D.A., Barnes, V.R., Sr. and Axhemi, A.A. Genes of the thymidine salvage pathway: thymine-7-hydroxylase from a Rhodotorula glutinis cDNA library and iso-orotate decarboxylase from Neurospora crassa. Biochim. Biophys Acta 1723 (2005) 256-264. [PMID: 15794921]
Accepted name: 2,4-dichlorophenoxyacetate dioxygenase
Reaction: 2,4-dichlorophenoxyacetate + 2-oxoglutarate + O2 = 2,4-dichlorophenol + glyoxylate + succinate + CO2
Other name(s): tfdA (gene name)
Systematic name: 2,4-dichlorophenoxyacetate,2-oxoglutarate:oxygen oxidoreductase (2,4-dichlorophenol-forming)
Comments: Requires Fe(II). The enzyme catalyses the first step in the bacterial degradation of 2,4-dichlorophenoxyacetate. Also acts on 4-chloro-2-methylphenoxyacetate.
References:
1. Streber, W.R., Timmis, K.N. and Zenk, M.H. Analysis, cloning, and high-level expression of 2,4-dichlorophenoxyacetate monooxygenase gene tfdA of Alcaligenes eutrophus JMP134. J. Bacteriol. 169 (1987) 2950-2955. [PMID: 3036764]
2. Fukumori, F. and Hausinger, R.P. Alcaligenes eutrophus JMP134 "2,4-dichlorophenoxyacetate monooxygenase" is an α-ketoglutarate-dependent dioxygenase. J. Bacteriol. 175 (1993) 2083-2086. [PMID: 8458850]
3. Fukumori, F. and Hausinger, R.P. Purification and characterization of 2,4-dichlorophenoxyacetate/α-ketoglutarate dioxygenase. J. Biol. Chem. 268 (1993) 24311-24317. [PMID: 8226980]
4. Hausinger, R.P. and Fukumori, F. Characterization of the first enzyme in 2,4-dichlorophenoxyacetic acid metabolism. Environ Health Perspect 103 Suppl 5 (1995) 37-39. [PMID: 8565907]
5. Hogan, D.A., Smith, S.R., Saari, E.A., McCracken, J. and Hausinger, R.P. Site-directed mutagenesis of 2,4-dichlorophenoxyacetic acid/α-ketoglutarate dioxygenase. Identification of residues involved in metallocenter formation and substrate binding. J. Biol. Chem. 275 (2000) 12400-12409. [PMID: 10777523]
6. Poh, R., Xia, X., Bruce, I.J. and Smith, A.R. 2,4-dichlorophenoxyacetate/α-ketoglutarate dioxygenases from Burkholderia cepacia 2a and Ralstonia eutropha JMP134. Microbios 105 (2001) 43-63. [PMID: 11368091]
7. Dunning Hotopp, J.C. and Hausinger, R.P. Probing the 2,4-dichlorophenoxyacetate/α-ketoglutarate dioxygenase substrate-binding site by site-directed mutagenesis and mechanism-based inactivation. Biochemistry 41 (2002) 9787-9794. [PMID: 12146944]
Accepted name: sulfoquinovose dioxygenase
Reaction: 6-sulfo-D-quinovose + O2 + 2-oxoglutarate = 6-dehydro-D-glucose + hydrogensulfite + succinate + CO2
Glossary: 6-sulfo-D-quinovose = sulfoquinovose = 6-deoxy-6-sulfo-D-glucopyranose
Other name(s): SQ dioxygenase; sqoD (gene name)
Systematic name: 6-sulfo-D-quinovose,2-oxoglutarate:oxygen oxidoreductase (sulfite-forming)
Comments: The enzyme, characterized from the marine bacterium Marinobacterium aestuarii, participates in a sulfolytic degradative pathway of sulfoquinovose by cleaving the carbon-sulfur bond. The enzyme requires Fe(II). cf. EC 1.1.1.390 (sulfoquinovose 1-dehydrogenase) and EC 1.14.14.181 (sulfoquinovose monooxygenase).
References:
1. Ye, Z., Wei, Y., Jiang, L. and Zhang, Y. Oxygenolytic sulfoquinovose degradation by an iron-dependent alkanesulfonate dioxygenase. iScience 26 (2023) 107803. [PMID: 37731605]
Accepted name: 2-nitrophenol 2-monooxygenase
Reaction: 2-nitrophenol + 2 NADPH + 2 H+ + O2 = catechol + nitrite + 2 NADP+ + H2O
(1a) 2-nitrophenol + NADPH + H+ + O2 = 1,2-benzoquinone + nitrite + NADP+ + H2O
(1b) 1,2-benzoquinone + NADPH + H+ = catechol + NADP+ (spontaneous)
For diagram of catechol biosynthesis, click here
Other name(s): 2-nitrophenol oxygenase; nitrophenol oxygenase; OnpA
Systematic name: 2-nitrophenol,NADPH:oxygen 2-oxidoreductase (2-hydroxylating, nitrite-forming)
Comments: Involved in the metabolism of nitro-aromatic compounds by bacteria. The enzyme contains a cytochrome b5 domain that is involved in the reaction, and binds FAD and heme b. It has been suggested that reaction (1b) is spontaneous only in vitro and is catalysed by a different enzyme (OnpB) in vivo.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc, CAS registry number: 104520-84-5
References:
1. Zeyer, J., Kocher, H.P. and Timmis, N. Influence of para-substituents on the oxidative metabolism of o-nitrophenols by Pseudomonas putida B2. Appl. Environ. Microbiol. 52 (1986) 334-339. [PMID: 3752997]
2. Xiao, Y., Zhang, J.J., Liu, H. and Zhou, N.Y. Molecular characterization of a novel ortho-nitrophenol catabolic gene cluster in Alcaligenes sp. strain NyZ215. J. Bacteriol. 189 (2007) 6587-6593. [PMID: 17616586]
3. Xiao, Y., Liu, T.T., Dai, H., Zhang, J.J., Liu, H., Tang, H., Leak, D.J. and Zhou, N.Y. OnpA, an unusual flavin-dependent monooxygenase containing a cytochrome b5 domain. J. Bacteriol. 194 (2012) 1342-1349. [PMID: 22267507]
Accepted name: trivalent organoarsenical oxidase
Reaction: methylarsonous acid + NADPH + O2 = methylarsonate + NADP+ + H2O
Glossary: roxarsone (III) = (4-hydroxy-3-nitrophenyl)arsonous acid
methylarsonous acid = methylarsonite
Other name(s): arsH (gene name)
Systematic name: trivalent organoarsenical,NADPH:oxygen oxidoreductase (pentavalent organoarsenical-forming)
Comments: Contains FMN. The enzyme, found in bacteria, detoxifies trivalent methylated and aromatic arsenicals such as methylarsonous acid, phenylarsonous acid and roxarsone (III) by oxidation to pentavalent species. Methylarsonous acid can be formed from the herbicide methylarsonate by EC 1.20.4.2, methylarsonate reductase.
References:
1. Chen, J., Bhattacharjee, H. and Rosen, B.P. ArsH is an organoarsenical oxidase that confers resistance to trivalent forms of the herbicide monosodium methylarsenate and the poultry growth promoter roxarsone. Mol. Microbiol. 96 (2015) 1042-1052. [PMID: 25732202]
2. Paez-Espino, A.D., Nikel, P.I., Chavarria, M. and de Lorenzo, V. ArsH protects Pseudomonas putida from oxidative damage caused by exposure to arsenic. Environ. Microbiol. 22 (2020) 2230-2242. [PMID: 32202357]
3. Sedlacek, V., Kryl, M. and Kucera, I. The ArsH protein product of the Paracoccus denitrificans ars operon has an activity of organoarsenic reductase and is regulated by a redox-responsive repressor. Antioxidants (Basel) 11 (2022) 902. [PMID: 35624766]
4. Kucera, I. and Sedlacek, V. Flavin-dependent enzymatic and photochemical interconversions between phenylarsonic and phenylarsonous acids. Biometals 38 (2025) 903-915. [PMID: 40240666]
[EC 2.1.1.55 Deleted entry: tRNA (adenine-N6-)-methyltransferase. The reaction has never been shown to take place (EC 2.1.1.55 created 1981, deleted 2026)]
Accepted name: 4-vinylphenol O-methyltransferase
Reaction: S-adenosyl-L-methionine + 4-vinylphenol = S-adenosyl-L-homocysteine + 4-vinylanisole
Glossary: 4-vinylanisole = 4-methoxystyrene = 1-ethenyl-4-methoxybenzene
Other name(s): 4VPMT1; 4VPMT2
Systematic name: 4-vinylphenol O-methyltransferase
Comments: Isolated from the insect Locusta migratoria (migratory locust). 4-Vinylanisole is the swarming pheromone for locusts.
References:
1. Guo, X., Gao, L., Li, S., Gao, J., Wang, Y., Lv, J., Wei, J., Yang, J., Ke, H., Ding, Q., Yang, J., Guo, F., Zhang, H., Lei, X. and Kang, L. Decoding 4-vinylanisole biosynthesis and pivotal enzymes in locusts. Nature 644 (2025) 420-429. [PMID: 40562929]
[EC 2.3.1.200 Transferred entry: lipoyl amidotransferase. Now classified as EC 2.3.1.204, lipoyl-[GcvH]:protein N-lipoyltransferase. (EC 2.3.1.200 created 2012, deleted 2026)]
Accepted name: lipoyl-[GcvH]:protein N-lipoyltransferase
Reaction: [glycine cleavage system H protein]-N6-dihydrolipoyl-L-lysine + a [lipoyl-carrier protein] = [glycine cleavage system H protein] + a [lipoyl-carrier protein]-N6-dihydrolipoyl-L-lysine
Glossary: glycine cleavage system H protein = GcvH
lipoic acid = 5-[(3R)-1,2-dithiolan-3-yl]pentanoic acid
Other name(s): LipL; octanoyl-[GcvH]:E2 amidotransferase; ywfL (gene name); octanoyl-[GcvH]:protein N-octanoyltransferase; [glycine cleavage system H]-N6-octanoyl-L-lysine:[lipoyl-carrier protein]-N6-L-lysine octanoyltransferase
Systematic name: [glycine cleavage system H protein]-N6-dihydrolipoyl-L-lysine:[lipoyl-carrier protein]-N6-L-lysine dihydrolipoyltransferase
Comments: The enzyme has been shown in multiple bacteria to catalyse the amidotransfer of the dihydrolipoyl moiety from either the H protein of the glycine cleavage system (EC 1.4.1.27) or the E2 component (dihydrolipoamide acetyltransferase) of the 2-oxoglutarate dehydrogenase system (EC 1.2.1.105) to the E2 component of other 2-oxoacid dehydrogenase systems: the pyruvate dehydrogenase system (EC 1.2.1.104), the branched-chain α-keto acid dehydrogenase system (EC 1.2.1.25), and the acetoin dehydrogenase system (EC 2.3.1.190).
Links to other databases: BRENDA, EXPASY, GENE, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Christensen, Q.H., Martin, N., Mansilla, M.C., de Mendoza, D. and Cronan, J.E. A novel amidotransferase required for lipoic acid cofactor assembly in Bacillus subtilis. Mol. Microbiol. 80 (2011) 350-363. [PMID: 21338421]
2. Christensen, Q.H., Hagar, J.A., O'Riordan, M.X. and Cronan, J.E. A complex lipoate utilization pathway in Listeria monocytogenes. J. Biol. Chem. 286 (2011) 31447-31456. [PMID: 21768091]
3. Martin, N., Christensen, Q.H., Mansilla, M.C., Cronan, J.E. and de Mendoza, D. A novel two-gene requirement for the octanoyltransfer reaction of Bacillus subtilis lipoic acid biosynthesis. Mol. Microbiol. 80 (2011) 335-349. [PMID: 21338420]
4. Rasetto, N.B., Lavatelli, A., Martin, N. and Mansilla, M.C. Unravelling the lipoyl-relay of exogenous lipoate utilization in Bacillus subtilis. Mol. Microbiol. 112 (2019) 302-316. [PMID: 31066113]
5. Cronan, J.E. Lipoic acid attachment to proteins: stimulating new developments. Microbiol. Mol. Biol. Rev. 88 (2024) e0000524. [PMID: 38624243]
Accepted name: conjugated bile acid:L-amino acid N-acyltransferase
Reaction: (1) glycocholate + an L-amino acid = an amino acid—bile acid amidate + glycine
(2) taurocholate + an L-amino acid = an amino acid—bile acid amidate + taurine
Other name(s): bsh (gene name)
Systematic name: conjugated bile acid:L-amino acid N-acyltransferase
Comments: Amino acid—bile acid amidates are formed in the gastrointestinal tract from bile acid conjugates of glycine or taurine. This is a second activity of the bacterial enzyme EC 3.5.1.24, choloylglycine hydrolase (also known as bile salt hydrolase).
References:
1. Rimal, B., Collins, S.L., Tanes, C.E., Rocha, E.R., Granda, M.A., Solanki, S., Hoque, N.J., Gentry, E.C., Koo, I., Reilly, E.R., Hao, F., Paudel, D., Singh, V., Yan, T., Kim, M.S., Bittinger, K., Zackular, J.P., Krausz, K.W., Desai, D., Amin, S., Coleman, J.P., Shah, Y.M., Bisanz, J.E., Gonzalez, F.J., Vanden Heuvel, J.P., Wu, G.D., Zemel, B.S., Dorrestein, P.C., Weinert, E.E. and Patterson, A.D. Bile salt hydrolase catalyses formation of amine-conjugated bile acids. Nature 626 (2024) 859-863. [PMID: 38326609]
Accepted name: [protein]-L-lysine N-acetyltransferase
Reaction: acetyl-CoA + a [protein]-L-lysine = CoA + a [protein]-N6-acetyl-L-lysine
Other name(s): Nε-lysine acetyltransferase; KAT; peptidyl-lysine N-acetyltransferase; protein-N6-acetyl-L-lysine:CoA acetyltranferase; protein-lysine Nε-acetyltransferase
Systematic name: acetyl-CoA:[protein]-L-lysine N6-acetyltransferase
Comments: This entry stands for enzymes that catalyse the acetylation of the N6 of lysine residues within multiple proteins. Most enzymes are specific for a subset of proteins, though it could be very large. For example, YiaC from Escherichia coli targets 391 unique lysine residues in 251 proteins [3]. The reaction is reversible and in some cases the enzyme acts as deacetylase [4]. Some specific cases include EC 2.3.1.48, histone acetyltransferase, EC 2.3.1.108, α-tubulin N-acetyltransferase, and EC 2.3.1.309, [β-tubulin]-L-lysine N-acetyltransferase.
References:
1. Castano-Cerezo, S., Bernal, V., Rohrig, T., Termeer, S. and Canovas, M. Regulation of acetate metabolism in Escherichia coli BL21 by protein Nε-lysine acetylation. Appl. Microbiol. Biotechnol. 99 (2015) 3533-3545. [PMID: 25524697]
2. Zhang, Q., Zhou, A., Li, S., Ni, J., Tao, J., Lu, J., Wan, B., Li, S., Zhang, J., Zhao, S., Zhao, G.P., Shao, F. and Yao, Y.F. Reversible lysine acetylation is involved in DNA replication initiation by regulating activities of initiator DnaA in Escherichia coli. Sci. Rep. 6 (2016) 30837. [PMID: 27484197]
3. Christensen, D.G., Meyer, J.G., Baumgartner, J.T., D'Souza, A.K., Nelson, W.C., Payne, S.H., Kuhn, M.L., Schilling, B. and Wolfe, A.J. Identification of novel protein lysine acetyltransferases in Escherichia coli. mBio 9 (2018) e01905-18. [PMID: 30352934]
4. Rajendran, A., Vaidya, K., Mendoza, J., Bridwell-Rabb, J. and Kamat, S.S. Functional annotation of ABHD14B, an orphan serine hydrolase enzyme. Biochemistry 59 (2020) 183-196. [PMID: 31478652]
Accepted name: aromatic amino acid N-acyltransferase
Reaction: (1) an acyl-CoA + L-tryptophan = an N-acyl-L-tryptophan + CoA
(2) an acyl-CoA + L-tyrosine = an N-acyl-L-tyrosine + CoA
(3) an acyl-CoA + L-phenylalanine = an N-acyl-L-phenylalanine + CoA
Glossary: an oxazolone = an oxazole compound with a keto group attached to the ring
an oxazole = an azole compound based on a five-membered heterocyclic aromatic skeleton with an oxygen and a nitrogen separated by one carbon
Other name(s): tyzA (gene name); oxzA (gene name); trzA (gene name)
Systematic name: acyl-CoA:aromatic amino acid N-acetyltransferase
Comments: The enzyme catalyses the first step in the biosynthesis of oxazolone compounds (phenazolones, tyrazolones, and tryptazolones), which have been reported from Gram-negative as well as Gram-positive bacteria. The enzymes from different organisms have different specificity for the amino acid substrate, as well as for the length of the acyl-CoA tail.
References:
1. de Rond, T., Asay, J.E. and Moore, B.S. Co-occurrence of enzyme domains guides the discovery of an oxazolone synthetase. Nat. Chem. Biol. 17 (2021) 794-799. [PMID: 34099916]
2. Grigg, J.C., Copp, J.N., Krekhno, J.MC., Liu, J., Ibrahimova, A. and Eltis, L.D. Deciphering the biosynthesis of a novel lipid in Mycobacterium tuberculosis expands the known roles of the nitroreductase superfamily. J. Biol. Chem. 299 (2023) 104924. [PMID: 37328106]
3. Kleetz, J., Grigg, J.C., Hassan, A.A., Ibtisam, A., Copp, J.N., Lian, J., Liu, J. and Eltis, L.D. The biosynthesis of N-acylated tryptazolone in Mycobacterium tuberculosis and related bacteria. J. Biol. Chem. 302 (2026) 111079. [PMID: 41429352]
Accepted name: tryptophan C-mannosyltransferase
Reaction: dolichyl β-D-mannosyl phosphate + L-tryptophyl-[protein] = dolichyl phosphate + 2-C-(α-D-mannosyl)-L-tryptophyl-[protein]
Other name(s): Dpy-19; dumpy-19; DPY19L1; DPY19L3
Systematic name: dolichyl β-D-mannosyl-phosphate:L-tryptophyl-[protein] 2-C-D-mannosyltransferase (configuration-inverting)
Comments: This enzyme transfers a mannose to the first tryptophan in a WxxW or WxxC consensus sequon of acceptor proteins and is related to the oligosaccharyltransferase family involved in protein N-glycosylation, which utilizes a dolichol diphosphate-linked oligosaccharide as the donor (EC 2.4.99.18, dolichyl-diphosphooligosaccharide—protein glycotransferase). Enzymes from Caenorhabditis elegans and mammals have been characterized.
References:
1. Buettner, F.F., Ashikov, A., Tiemann, B., Lehle, L. and Bakker, H. C. elegans DPY-19 is a C-mannosyltransferase glycosylating thrombospondin repeats. Mol. Cell 50 (2013) 295-302. [PMID: 23562325]
2. Shcherbakova, A., Tiemann, B., Buettner, F.F. and Bakker, H. Distinct C-mannosylation of netrin receptor thrombospondin type 1 repeats by mammalian DPY19L1 and DPY19L3. Proc. Natl. Acad. Sci. USA 114 (2017) 2574-2579. [PMID: 28202721]
3. Bloch, J.S., John, A., Mao, R., Mukherjee, S., Boilevin, J., Irobalieva, R.N., Darbre, T., Scott, N.E., Reymond, J.L., Kossiakoff, A.A., Goddard-Borger, E.D. and Locher, K.P. Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase. Nat. Chem. Biol. 19 (2023) 575-584. [PMID: 36604564]
Accepted name: L-histidine 2-aminobutanoyltransferase
Reaction: S-adenosyl-L-methionine + L-histidine = N-[(3S)-3-amino-3-carboxypropyl]-L-histidine + S-methyl-5'-thioadenosine
Other name(s): cntL (gene name); smtA3 (gene name)
Systematic name: S-adenosyl-L-methionine:L-histidine N-[(3S)-3-amino-3-carboxypropyl]-transferase
Comments: The enzyme, characterized from the bactreria Pseudomonas aeruginosa and Yersinia pestis, is similar to EC 2.5.1.152, D-histidine 2-aminobutanoyltransferase, but is specific for L-histidine. The enzyme participates in the biosynthesis of the opine metallophores pseudopaline and yersinopine, respectively, in the two organisms.
References:
1. McFarlane, J.S. and Lamb, A.L. Biosynthesis of an opine metallophore by Pseudomonas aeruginosa. Biochemistry 56 (2017) 5967-5971. [PMID: 29091735]
2. McFarlane, J.S., Davis, C.L. and Lamb, A.L. Staphylopine, pseudopaline, and yersinopine dehydrogenases: A structural and kinetic analysis of a new functional class of opine dehydrogenase. J. Biol. Chem. 293 (2018) 8009-8019. [PMID: 29618515]
Accepted name: phenolic phosphate synthase
Reaction: (1) genistein + ATP + H2O = genistein 7-O-phosphate + AMP + phosphate
(2) genistein + ATP + H2O = genistein 4'-O-phosphate + AMP + phosphate
Glossary: genistein = 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one
Other name(s): polyphenol water dikinase; polyphenol phosphotransferase; flavonoid phosphate synthetase; benzopyrone phosphate synthetase; PPS; phenolic phosphate synthetase; fpsC (gene name); yvkC (gene name)
Systematic name: ATP:polyphenol, water phosphotransferase
Comments: The enzyme, characterized from the bacterium Bacillus subtilis, is a promiscuous phosphotransferase that catalyses mono-O-phosphorylation of a broad spectrum of phenolic and polyphenolic substrates, including flavonoid classes such as isoflavones, flavones, flavonols, flavanones, and flavonolignans, as well as structurally varied scaffolds like stilbenoids, curcuminoids, chalcones, anthraquinones, coumestans, and coumarins. The reaction is carried out by a ping-pong mechanism involving transient autophosphorylation of a histidine residue. Polyphenols are usually phosphorylated at different sites, producing a mixture of mono-phosphorylated products.
References:
1. Hsu, C., Tsai, H.Y., Chang, C.F., Yang, C.C. and Su, N.W. Discovery of a novel phosphotransferase from Bacillus subtilis that phosphorylates a broad spectrum of flavonoids. Food Chem 400 (2023) 134001. [PMID: 36084586]
2. Hsu, C., Tsai, H.Y., Chen, S.D., Chang, C.F. and Su, N.W. Molecular insights into a promiscuous dikinase catalyzing monophosphorylation of structurally diverse natural polyphenols. ACS Catalysis 15 (2025) 13179-13191.
Accepted name: tRNA-2-methylthio-N6-dimethylallyladenosine synthase
Reaction: N6-(3-methylbut-2-en-1-yl)-adenine37 in tRNA + a [3Fe-4S] iron-sulfur cluster + 2 S-adenosyl-L-methionine + reduced electron acceptor = N6-(3-methylbut-2-en-1-yl)-2-(methylsulfanyl)adenine37 in tRNA + S-adenosyl-L-homocysteine + a [3Fe-3S] iron-sulfur cluster + L-methionine + 5'-deoxyadenine + electron acceptor
For diagram of reaction click here
Glossary: N6-(3-methylbut-2-en-1-yl)-adenine37 in tRNA = N6-dimethylallyladenine37 in tRNA
Other name(s): MiaB; 2-methylthio-N-6-isopentenyl adenosine synthase; tRNA-i6A37 methylthiotransferase
Systematic name: tRNA N6-(3-methylbut-2-en-1-yl)-adenine37:[3Fe-4S] iron-sulfur cluster,S-adenosyl-L-methionine C2-(methylsulfanyl)transferase
Comments: The enzyme is a member of the AdoMet radical (radical SAM) family. It contains one [4Fe-4S] cluster (the main cluster) and one [3Fe-4S] cluster (the auxiliary cluster). The reaction is thought to take place in two steps. In the first step, one molecule of SAM is used to methylate a bridging μ-sulfido ion of the auxiliary cluster, forming a thio-methyl group. In the second step, a second SAM molecule is cleaved to a 5'-deoxyadenosyl 5'-radical, which abstracts the C2 hydrogen of the substrate, and the thio-methyl group is transferred from the auxiliary cluster to the radical-activated carbon in the tRNA substrate. The auxiliary cluster is left in an inactive [3Fe-3S] state and must be repaired or replaced before the enzyme could catalyse the next round.
Links to other databases: BRENDA, EXPASY, GENE, KEGG, MetaCyc, PDB, CAS registry number
References:
1. Pierrel, F., Bjork, G.R., Fontecave, M. and Atta, M. Enzymatic modification of tRNAs: MiaB is an iron-sulfur protein. J. Biol. Chem. 277 (2002) 13367-13370. [PMID: 11882645]
2. Pierrel, F., Hernandez, H.L., Johnson, M.K., Fontecave, M. and Atta, M. MiaB protein from Thermotoga maritima. Characterization of an extremely thermophilic tRNA-methylthiotransferase. J. Biol. Chem. 278 (2003) 29515-29524. [PMID: 12766153]
3. Hernandez, H.L., Pierrel, F., Elleingand, E., Garcia-Serres, R., Huynh, B.H., Johnson, M.K., Fontecave, M. and Atta, M. MiaB, a bifunctional radical-S-adenosylmethionine enzyme involved in the thiolation and methylation of tRNA, contains two essential [4Fe-4S] clusters. Biochemistry 46 (2007) 5140-5147. [PMID: 17407324]
4. Landgraf, B.J., Arcinas, A.J., Lee, K.H. and Booker, S.J. Identification of an intermediate methyl carrier in the radical S-adenosylmethionine methylthiotransferases RimO and MiaB. J. Am. Chem. Soc. 135 (2013) 15404-15416. [PMID: 23991893]
5. Zhang, B., Arcinas, A.J., Radle, M.I., Silakov, A., Booker, S.J. and Krebs, C. First step in catalysis of the radical S-adenosylmethionine methylthiotransferase MiaB yields an intermediate with a [3Fe-4S]0-like auxiliary cluster. J. Am. Chem. Soc. 142 (2020) 1911-1924. [PMID: 31899624]
6. Esakova, O.A., Grove, T.L., Yennawar, N.H., Arcinas, A.J., Wang, B., Krebs, C., Almo, S.C. and Booker, S.J. Structural basis for tRNA methylthiolation by the radical SAM enzyme MiaB. Nature 597 (2021) 566-570. [PMID: 34526715]
Accepted name: L-galactono-1,5-lactonase
Reaction: L-galactono-1,5-lactone + H2O = L-galactonate
Other name(s): lgaB (gene name); Bvu0220
Systematic name: L-glucono-1,5-lactone lactonohydrolase
Comments: The enzyme catalyses a step in the bacterial L-galactose utilization metabolic pathway. The upstream enzyme, EC 1.1.1.445 L-galactose 1-dehydrogenase (NADP+), produces L-galactono-1,5-lactone, which is spontaneously converted to L-galactono-1,4-lactone. However, the enzyme from Phocaeicola vulgatus hydrolyses L-galactono-1,5-lactone 300-fold faster than L-galactono-1,4-lactone. The product, L-galactonate, is further degraded by L-galactonate 5-dehydrogenase (EC 1.1.1.414).
References:
1. Hobbs, M.E., Williams, H.J., Hillerich, B., Almo, S.C. and Raushel, F.M. L-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota. Biochemistry 53 (2014) 4661-4670. [PMID: 24963813]
Accepted name: phosphatidate phosphatase
Reaction: a 1,2-diacylglycerol 3-phosphate + H2O = a 1,2-diacyl-sn-glycerol + phosphate
Glossary: a 1,2-diacylglycerol 3-phosphate = a 3-sn-phosphatidate
a 1,2-diacyl-sn-glycerol = diacylglycerol = DAG
Other name(s): phosphatic acid phosphatase; acid phosphatidyl phosphatase; phosphatic acid phosphohydrolase; PAP; Lipin; LPIN1 (gene name); LPIN2 (gene name); LPIN3 (gene name)
Systematic name: diacylglycerol-3-phosphate phosphohydrolase
Comments: This enzyme catalyses the Mg2+-dependent dephosphorylation of a 1,2-diacylglycerol-3-phosphate, yielding a 1,2-diacyl-sn-glycerol (DAG), the substrate for de novo lipid synthesis via the Kennedy pathway and for the synthesis of triacylglycerol. In lipid signalling, the enzyme generates a pool of DAG to be used for protein kinase C activation. The mammalian enzymes are known as lipins. cf. EC 3.1.3.106, 2-lysophosphatidate phosphatase, and EC 3.1.3.113, phospholipid phosphatase.
Links to other databases: BRENDA, EXPASY, GENE, KEGG, MetaCyc, PDB, CAS registry number: 9025-77-8
References:
1. Smith, S.W., Weiss, S.B. and Kennedy, E.P. The enzymatic dephosphorylation of phosphatidic acids. J. Biol. Chem. 228 (1957) 915-922. [PMID: 13475370]
2. Donkor, J., Sariahmetoglu, M., Dewald, J., Brindley, D.N. and Reue, K. Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns. J. Biol. Chem. 282 (2007) 3450-3457. [PMID: 17158099]
3. Carman, G.M. and Han, G.S. Phosphatidic acid phosphatase, a key enzyme in the regulation of lipid synthesis. J. Biol. Chem. 284 (2009) 2593-2597. [PMID: 18812320]
4. Han, G.S. and Carman, G.M. Characterization of the human LPIN1-encoded phosphatidate phosphatase isoforms. J. Biol. Chem. 285 (2010) 14628-14638. [PMID: 20231281]
5. Eaton, J.M., Mullins, G.R., Brindley, D.N. and Harris, T.E. Phosphorylation of lipin 1 and charge on the phosphatidic acid head group control its phosphatidic acid phosphatase activity and membrane association. J. Biol. Chem. 288 (2013) 9933-9945. [PMID: 23426360]
6. Li, T.Y., Song, L., Sun, Y., Li, J., Yi, C., Lam, S.M., Xu, D., Zhou, L., Li, X., Yang, Y., Zhang, C.S., Xie, C., Huang, X., Shui, G., Lin, S.Y., Reue, K. and Lin, S.C. Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate. Nat. Commun. 9 (2018) 1916. [PMID: 29765047]
Accepted name: phospholipid phosphatase
Reaction: a phospholipid + H2O = a lipid + phosphate
Other name(s): lipid phosphate phosphatase; type 2 phosphatidic acid phosphatase; PAP2; PLPP1 (gene name); PLPP2 (gene name); PLPP3 (gene name); PLPP4 (gene name)
Systematic name: phospholipid phosphohydrolase
Comments: The enzyme is a Mg2+-independent phosphatase that catalyses the dephosphorylation of a broad spectrum of glycerolipid and sphingolipid phosphate esters, including phosphatidate, lysophosphatidate, diacylglycerol pyrophosphate, sphingosine 1-phosphate, and ceramide 1-phosphate. cf. EC 3.1.3.4, phosphatidate phosphatase, EC 3.1.3.106, 2-lysophosphatidate phosphatase, EC 3.1.3.114, sphingoid-base-1-phosphate phosphatase, and EC 3.1.3.115, ceramide-1-phosphate phosphatase.
References:
1. Kai, M., Wada, I., Imai Si, Sakane, F. and Kanoh, H. Cloning and characterization of two human isozymes of Mg2+-independent phosphatidic acid phosphatase. J. Biol. Chem. 272 (1997) 24572-24578. [PMID: 9305923]
2. Hooks, S.B., Ragan, S.P. and Lynch, K.R. Identification of a novel human phosphatidic acid phosphatase type 2 isoform. FEBS Lett. 427 (1998) 188-192. [PMID: 9607309]
3. Roberts, R., Sciorra, V.A. and Morris, A.J. Human type 2 phosphatidic acid phosphohydrolases. Substrate specificity of the type 2a, 2b, and 2c enzymes and cell surface activity of the 2a isoform. J. Biol. Chem. 273 (1998) 22059-22067. [PMID: 9705349]
4. Waggoner, D.W., Xu, J., Singh, I., Jasinska, R., Zhang, Q.X. and Brindley, D.N. Structural organization of mammalian lipid phosphate phosphatases: implications for signal transduction. Biochim. Biophys Acta 1439 (1999) 299-316. [PMID: 10425403]
5. Roberts, R.Z. and Morris, A.J. Role of phosphatidic acid phosphatase 2a in uptake of extracellular lipid phosphate mediators. Biochim. Biophys Acta 1487 (2000) 33-49. [PMID: 10962286]
6. Zhao, Y., Kalari, S.K., Usatyuk, P.V., Gorshkova, I., He, D., Watkins, T., Brindley, D.N., Sun, C., Bittman, R., Garcia, J.G., Berdyshev, E.V. and Natarajan, V. Intracellular generation of sphingosine 1-phosphate in human lung endothelial cells: role of lipid phosphate phosphatase-1 and sphingosine kinase 1. J. Biol. Chem. 282 (2007) 14165-14177. [PMID: 17379599]
7. Tang, X., Benesch, M.G. and Brindley, D.N. Lipid phosphate phosphatases and their roles in mammalian physiology and pathology. J. Lipid Res. 56 (2015) 2048-2060. [PMID: 25814022]
Accepted name: sphingoid-base-1-phosphate phosphatase
Reaction: a sphingoid base 1-phosphate + H2O = a sphingoid base + phosphate
Other name(s): S1P phosphatase; sphingosine-1-phosphate phosphatase; long-chain base-1-phosphate phosphatase; dihydrosphingosine-1-phosphate phosphatase; LCB3 (gene name); YSR3 (gene name); SGPP1 (gene name); SGPP2 (gene name)
Systematic name: sphingoid base 1-phosphate phosphohydrolase
Comments: The enzyme specifically dephosphorylates long-chain sphingoid base phosphates such as sphingosine 1-phosphate, sphinganine 1-phosphate, and phytosphingosine 1-phosphate. It does not act on ceramide 1-phosphate, lysophosphatidic acids, or phosphatidic acids. cf. EC 3.1.3.4, phosphatidate phosphatase, EC 3.1.3.106, 2-lysophosphatidate phosphatase, and EC 3.1.3.113, phospholipid phosphatase.
References:
1. Mandala, S.M., Thornton, R., Tu, Z., Kurtz, M.B., Nickels, J., Broach, J., Menzeleev, R. and Spiegel, S. Sphingoid base 1-phosphate phosphatase: a key regulator of sphingolipid metabolism and stress response. Proc. Natl. Acad. Sci. USA 95 (1998) 150-155. [PMID: 9419344]
2. Mao, C., Saba, J.D. and Obeid, L.M. The dihydrosphingosine-1-phosphate phosphatases of Saccharomyces cerevisiae are important regulators of cell proliferation and heat stress responses. Biochem. J. 342 Pt 3 (1999) 667-675. [PMID: 10477278]
3. Ogawa, C., Kihara, A., Gokoh, M. and Igarashi, Y. Identification and characterization of a novel human sphingosine-1-phosphate phosphohydrolase, hSPP2. J. Biol. Chem. 278 (2003) 1268-1272. [PMID: 12411432]
4. Giussani, P., Maceyka, M., Le Stunff, H., Mikami, A., Lepine, S., Wang, E., Kelly, S., Merrill, A.H., Jr., Milstien, S. and Spiegel, S. Sphingosine-1-phosphate phosphohydrolase regulates endoplasmic reticulum-to-golgi trafficking of ceramide. Mol. Cell Biol. 26 (2006) 5055-5069. [PMID: 16782891]
Accepted name: ceramide-1-phosphate phosphatase
Reaction: a ceramide 1-phosphate + H2O = a ceramide + phosphate
Other name(s): C1PP; C1P phosphatase
Systematic name: ceramide-1-phosphate phosphohydrolase
Comments: Ceramide 1-phosphate, produced by EC 2.7.1.138, ceramide kinase, is dephosphorylated in mammalian tissue. EC 3.1.3.113, phospholipid phosphatase, has been shown to catalyse this activity in vitro.
References:
1. Shinghal, R., Scheller, R.H. and Bajjalieh, S.M. Ceramide 1-phosphate phosphatase activity in brain. J. Neurochem. 61 (1993) 2279-2285. [PMID: 8245978]
2. Boudker, O. and Futerman, A.H. Detection and characterization of ceramide-1-phosphate phosphatase activity in rat liver plasma membrane. J. Biol. Chem. 268 (1993) 22150-22155. [PMID: 8408075]
3. Waggoner, D.W., Gomez-Munoz, A., Dewald, J. and Brindley, D.N. Phosphatidate phosphohydrolase catalyzes the hydrolysis of ceramide 1-phosphate, lysophosphatidate, and sphingosine 1-phosphate. J. Biol. Chem. 271 (1996) 16506-16509. [PMID: 8663293]
4. Roberts, R., Sciorra, V.A. and Morris, A.J. Human type 2 phosphatidic acid phosphohydrolases. Substrate specificity of the type 2a, 2b, and 2c enzymes and cell surface activity of the 2a isoform. J. Biol. Chem. 273 (1998) 22059-22067. [PMID: 9705349]
5. Brindley, D.N., Xu, J., Jasinska, R. and Waggoner, D.W. Analysis of ceramide 1-phosphate and sphingosine-1-phosphate phosphatase activities. Methods Enzymol. 311 (2000) 233-244. [PMID: 10563330]
Accepted name: phosphatidylethanolamine phospholipase C
Reaction: a phosphatidylethanolamine + H2O = a 1,2-diacyl-sn-glycerol + O-phosphoethanolamine
Other name(s): phosphatidylethanolamine-specific phospholipase C; PE-PLC; SMSr; SAMD8 (gene name); SMS1 (gene name)
Systematic name: phosphatidylethanolamine ethanolaminephosphohydrolase
Comments: This activity, which is similar to that of EC 3.1.4.3, phospholipase C, has been characterized from mammalian cells [1-4]. Multiple enzymes have been shown to catalyse this activity, including the human membrane-bound sphingomyelin synthase-related protein (SMSr, gene name; SAMD8) [6-8,] sphingomyelin synthase 1 (SMS1, gene name; SGMS1) [9] (cf. EC 2.7.8.27, sphingomyelin synthase), and the cytosolic phosphoethanolamine/phosphocholine phosphatase (gene name PHOSPHO1) [11]. Minor activity was also observed by sphingomyelin synthase 2 (SMS2, gene name; SGMS2) [10].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number
References:
1. Hafez, M.M. and Costlow, M.E. Phosphatidylethanolamine turnover is an early event in the response of NB2 lymphoma cells to prolactin. Exp. Cell Res. 184 (1989) 37-43. [PMID: 2507337]
2. Kiss, Z. and Anderson, W.B. ATP stimulates the hydrolysis of phosphatidylethanolamine in NIH 3T3 cells. Potentiating effects of guanosine triphosphates and sphingosine. J. Biol. Chem. 265 (1990) 7345-7350. [PMID: 2185245]
3. Kiss, Z., Crilly, K. and Chattopadhyay, J. Ethanol potentiates the stimulatory effects of phorbol ester, sphingosine and 4-hydroxynonenal on the hydrolysis of phosphatidylethanolamine in NIH 3T3 cells. Eur. J. Biochem. 197 (1991) 785-790. [PMID: 2029907]
4. Kiss, Z. The long-term combined stimulatory effects of ethanol and phorbol ester on phosphatidylethanolamine hydrolysis are mediated by a phospholipase C and prevented by overexpressed α-protein kinase C in fibroblasts. Eur. J. Biochem. 209 (1992) 467-473. [PMID: 1327780]
5. Kiss, Z. and Tomono, M. Compound D609 inhibits phorbol ester-stimulated phospholipase D activity and phospholipase C-mediated phosphatidylethanolamine hydrolysis. Biochim. Biophys Acta 1259 (1995) 105-108. [PMID: 7492608]
6. Murakami, C. and Sakane, F. Sphingomyelin synthase-related protein generates diacylglycerol via the hydrolysis of glycerophospholipids in the absence of ceramide. J. Biol. Chem. 296 (2021) 100454. [PMID: 33621517]
7. Chiang, Y.P., Li, Z., Chen, Y., Cao, Y. and Jiang, X.C. Sphingomyelin synthase related protein is a mammalian phosphatidylethanolamine phospholipase C. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1866 (2021) 159017. [PMID: 34332077]
8. Hu, K., Zhang, Q., Chen, Y., Yang, J., Xia, Y., Rao, B., Li, S., Shen, Y., Cao, M., Lu, H., Qin, A., Jiang, X.C., Yao, D., Zhao, J., Zhou, L. and Cao, Y. Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis. Nat. Struct. Mol. Biol. (2024) . [PMID: 38388831]
9. Suzuki, R., Murakami, C., Dilimulati, K., Atsuta-Tsunoda, K., Kawai, T. and Sakane, F. Human sphingomyelin synthase 1 generates diacylglycerol in the presence and absence of ceramide via multiple enzymatic activities. FEBS Lett. 597 (2023) 2672-2686. [PMID: 37715942]
10. Murakami, C., Dilimulati, K., Atsuta-Tsunoda, K., Kawai, T., Inomata, S., Hijikata, Y., Sakai, H. and Sakane, F. Multiple activities of sphingomyelin synthase 2 generate saturated fatty acid- and/or monounsaturated fatty acid-containing diacylglycerol. J. Biol. Chem. 300 (2024) 107960. [PMID: 39510177]
11. Murakami, C., Atsuta-Tsunoda, K., Inomata, S., Kawai, T., Hijikata, Y., Dilimulati, K., Sakai, H. and Sakane, F. Human PHOSPHO1 exhibits phosphatidylcholine- and phosphatidylethanolamine-phospholipase C activities and interacts with diacylglycerol kinase δ. FEBS Lett. 599 (2025) 1169-1186. [PMID: 39992810]
Accepted name: sucrose α-glucosidase
Reaction: Hydrolysis of sucrose and maltose by an α-D-glucosidase-type action
Other name(s): sucrose α-glucohydrolase; sucrase (ambiguous); sucrase-isomaltase; intestinal sucrase; SI (gene name)
Systematic name: sucrose-α-D-glucohydrolase
Comments: The enzyme, found in animals, consists of two glycosyl hydrolase 31 domains side by side. The N-terminal domain degrades isomaltose (cf. EC 3.2.1.10, oligo-1,6-glucosidase), while the C-terminal side degrades sucrose. The enzyme recognizes and hydrolyses the α-D-glucoside side of the sucrose molecule (a different enzyme, EC 3.2.1.26, β-fructofuranosidase, recognizes and hydrolyses the fructofuranoside group on the opposite side of sucrose).
Links to other databases: BRENDA, EXPASY, GENE, KEGG, MetaCyc, PDB, CAS registry number: 37288-39-4
References:
1. Conklin, K.A., Yamashiro, K.M. and Gray, G.M. Human intestinal sucrase-isomaltase. Identification of free sucrase and isomaltase and cleavage of the hybrid into active distinct subunits. J. Biol. Chem. 250 (1975) 5735-5741. [PMID: 807575]
2. 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. [PMID: 291933]
3. Kolinska, J. and Kraml, J. Separation and characterization of sucrose-isomaltase and of glucoamylase of rat intestine. Biochim. Biophys. Acta 284 (1972) 235-247. [PMID: 5073761]
4. Sigrist, H., Ronner, P. and Semenza, G. A hydrophobic form of the small-intestinal sucrase-isomaltase complex. Biochim. Biophys. Acta 406 (1975) 433-446. [PMID: 1182172]
5. 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]
6. Takesue, Y. Purification and properties of rabbit intestinal sucrase. J. Biochem. (Tokyo) 65 (1969) 545-552. [PMID: 5804876]
7. Sim, L., Willemsma, C., Mohan, S., Naim, H.Y., Pinto, B.M. and Rose, D.R. Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains. J. Biol. Chem. 285 (2010) 17763-17770. [PMID: 20356844]
Accepted name: arabinogalactan L-arabinofuranosyl-α-(1,3)-D-galactopyranoside arabinofuranosidase
Reaction: Hydrolysis of α-L-Araf-(1→3)-D-Galp bonds in side chains of the non-reducing termini of type II arabinogalactan attached to proteins.
Glossary: Araf = arabinofuranose
Arap = arabinopyranose
Galp = galactopyranose
Other name(s): 3-O-α-D-galactosyl-α-L-arabinofuranosidase; β-arabino-oligosaccharide 3-O-β-L-arabinopyranosyl-α-L-arabinofuranoside; type II arabinogalactan exo α-(1,3)-[α-D-galactosyl-(1→3)-L-arabinofuranose] hydrolase (non-reducing end); arabinogalactan exo α-(1,3)-α-D-galactosyl-(1→3)-L-arabinofuranosidase (non-reducing end)
Systematic name: type II arabinogalactan α-(1,3)-[α-L-arabinofuranosyl-(1→3)-D-galactopyranoside] hydrolase
Comments: The enzyme hydrolyses L-Araf-(1→3)-D-Galp bonds in different side chains of the non-reducing termini of arabinogalactan polysaccharides. The enzyme from the bacterium Bifidobacterium longum is particularly active with gum arabic arabinogalactan, a type II arabinogalactan produced by acacia trees. It acts on α-D-Galp-(1→3)-α-L-Araf-(1→3)-D-Galp side chains, releasing α-D-Galp-(1→3)-L-Araf disaccharides [1], and can also act (with much lower activity) on β-L-Arap-(1→3)-L-Araf-(1→3)-D-Galp side chains, releasing β-L-Arap-(1→3)-L-Araf disaccharides. The enzyme from Bifidobacterium catenulatum has wider specificity and can release longer oligosaccharides with the formula (β-L-Araf-(1→2)-)n-β-L-Arap-(1→3)-α-L-Araf (n = 0-3) [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Sasaki, Y., Horigome, A., Odamaki, T., Xiao, J.Z., Ishiwata, A., Ito, Y., Kitahara, K. and Fujita, K. Novel 3-O-α-D-galactosyl-α-L-arabinofuranosidase for the assimilation of gum arabic arabinogalactan protein in Bifidobacterium longum subsp. longum. Appl. Environ. Microbiol. 87 (2021) e02690-20. [PMID: 33674431]
2. Sasaki, Y., Matsuo, A., Hashiguchi, M., Fujimura, K., Koshino, H., Tanaka, K., Ito, Y., Kitahara, K., Ishiwata, A. and Fujita, K. Structural analysis of gum arabic side chains from Acacia seyal released by bifidobacterial β-arabino-oligosaccharide 3-O-β-L-arabinopyranosyl-α-L-arabinofuranosidase. Carbohydr. Polym. 349 (2025) 122965. [PMID: 39643419]
Accepted name: exo-chitodextrinase (reducing end)
Reaction: Hydrolysis of (1→4)-β-D-GlcNAc residues from the reducing end of oligosaccharides (GlcNAc)n → (GlcNAc)n-1 + GlcNAc
Other name(s): reducing-end GlcNAc-releasing chitin oligosaccharide hydrolase; MoChia1
Systematic name: N-acetyl-β-D-glucosaminyl-(1→4)-N-acetyl-β-D-glucosamine reducing-end N-acetyl-β-D-glucosaminohydrolase
Comments: The enzyme, originally isolated from the bacterium Pyricularia oryzae, specifically recognizes the reducing end β-anomer of chitin oligosaccharides with a degree of polymerization of at least 3 [(GlcNAc)n (n≥3)] and releases the terminal GlcNAc unit, leaving the new reducing end in the β configuration. It has barely detectable activity toward chitin polymer. This enzyme is distinct from exo-chitinase (reducing end) (EC 3.2.1.201), which releases disaccharide unit from the reduing end of chitin and chitodextrins (chitin oligosaccharides). cf. EC 3.2.1.202, endo-chitodextrinase.
References:
1. Ohnuma, T., Imaoka, S., Kataoka, C., Yoshimoto, T., Okada, R., Takeda, T., Fukamizo, T., Sakuda, S. and Ogata, M. MoChia1 is a GH18 reducing-end GlcNAc-releasing chitin oligosaccharide hydrolase from the rice blast fungus Magnaporthe oryzae. J. Biol. Chem. 302 (2026) 111462. [PMID: 41999891]
[EC 3.8.1.6 Deleted entry: 4-chlorobenzoate dehalogenase. This activity has been shown to be identical to EC 3.8.1.7. (EC 3.8.1.6 created 1989, modified 1999, deleted 2026)]
Accepted name: tetrathionate hydrolase
Reaction: tetrathionate + H2O = sulfate + thiosulfate + sulfur (overall reaction)
(1a) tetrathionate + H2O = disulfanidesulfonate + sulfate
(1b) disulfanidesulfonate = thiosulfate + sulfur (spontaneous)
Glossary: tetrathionate = disulfanedisulfonate
disulfanidesulfonate = disulfane monosulfonate
Other name(s): tetH (gene name)
Systematic name: tetrathionate sulfohydrolase
Comments: The enzyme, isolated from various acidophilic bacterial and archaeal species, has pH optima in the acidic range. The initial products are sulfate and disulfane monosulfonate. Though the latter is known to decompose spontaneously to sulfur and thiosulfate, it has been proposed that it can also react with itself, resulting in successive chain elongation leading to the production of elemental sulfur and sulfite.
References:
1. De Jong, G.A., Hazeu, W., Bos, P. and Kuenen, J.G. Isolation of the tetrathionate hydrolase from Thiobacillus acidophilus. Eur. J. Biochem. 243 (1997) 678-683. [PMID: 9057831]
2. Bugaytsova, Z. and Lindstrom, E.B. Localization, purification and properties of a tetrathionate hydrolase from Acidithiobacillus caldus. Eur. J. Biochem. 271 (2004) 272-280. [PMID: 14717695]
3. Kanao, T., Matsumoto, C., Shiraga, K., Yoshida, K., Takada, J. and Kamimura, K. Recombinant tetrathionate hydrolase from Acidithiobacillus ferrooxidans requires exposure to acidic conditions for proper folding. FEMS Microbiol. Lett. 309 (2010) 43-47. [PMID: 20546308]
4. Protze, J., Muller, F., Lauber, K., Nass, B., Mentele, R., Lottspeich, F. and Kletzin, A. An extracellular tetrathionate hydrolase from the thermoacidophilic archaeon Acidianus ambivalens with an activity optimum at pH 1. Front Microbiol. 2 (2011) 68. [PMID: 21747790]
Accepted name: steroid 17,20-aldolase
Reaction: cortisol = 11β-hydroxyandrostenedione + glycolaldehyde
Other name(s): steroid-17,20-desmolase; steroid transketolase; desAB (gene names)
Systematic name: cortisol glycolaldehyde-lyase [11β-hydroxyandrostenedione-forming]
Comments: Requires thiamine diphosphoate and Mn2+. The enzyme, characterized from the bacterium Clostridium scindens, removes the side-chain of 17,21-dihydroxy 20-oxosteroids. The enzyme has been shown to act on cortisol, 11-desoxycortisol, and prednisone.
References:
1. Bokkenheuser, V.D., Winter, J., Morris, G.N. and Locascio, S. Steroid desmolase synthesis by Eubacterium desmolans and Clostridium cadavaris. Appl. Environ. Microbiol. 52 (1986) 1153-1156. [PMID: 3466571]
2. Krafft, A.E., Winter, J., Bokkenheuser, V.D. and Hylemon, P.B. Cofactor requirements of steroid-17-20-desmolase and 20α-hydroxysteroid dehydrogenase activities in cell extracts of Clostridium scindens. J. Steroid Biochem. 28 (1987) 49-54. [PMID: 3475510]
3. Devendran, S., Mythen, S.M. and Ridlon, J.M. The desA and desB genes from Clostridium scindens ATCC 35704 encode steroid-17,20-desmolase. J. Lipid Res. 59 (2018) 1005-1014. [PMID: 29572237]
4. Ly, L.K., Rowles, J.L., 3rd, Paul, H.M., Alves, J.MP., Yemm, C., Wolf, P.M., Devendran, S., Hudson, M.E., Morris, D.J., Erdman, J.W., Jr. and Ridlon, J.M. Bacterial steroid-17,20-desmolase is a taxonomically rare enzymatic pathway that converts prednisone to 1,4-androstanediene-3,11,17-trione, a metabolite that causes proliferation of prostate cancer cells. J. Steroid Biochem. Mol. Biol. 199 (2020) 105567. [PMID: 31870912]
Accepted name: 2'-cyclic-ADP-D-ribose synthase
Reaction: NAD+ = (1''-2')-cyclic adenosine diphosphate-β-D-ribose + nicotinamide
Glossary: (1''-2')-cyclic adenosine diphosphate-β-D-ribose = 1,2'-anhydroadenine(5')diphosphate(5)-β-D-ribose = 1''-2' glycocyclic ADP-β-D-ribose = (1''-2')-cyclic ADP-β-D-ribose = 2'-cADPR = 1''-2' gcADPR = v-cADPR
Other name(s): 2'cADPR synthase; AbTIR; L6 (gene name); ROQ1 (gene name)
Systematic name: NAD+ lyase [(1''-2')-cyclic adenosine diphosphate-β-D-ribose-forming]
Comments: The enzyme, found in plants and bacteria, contains a TIR (Toll/interleukin-1 receptor) domain. Activity requires self-association into larger aggregates. In plants (1''-2')-cyclic adenosine diphosphate-β-D-ribose triggers localized cell death in response to infections [1-3]. The bacterial enzyme was shown to form filamentous structures, with substrate molecules present between the monomers [4]. cf. EC 4.3.99.7, 3'-cyclic-ADP-D-ribose synthase, and EC 3.2.2.6, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase.
References:
1. Horsefield, S., Burdett, H., Zhang, X., Manik, M.K., Shi, Y., Chen, J., Qi, T., Gilley, J., Lai, J.S., Rank, M.X., Casey, L.W., Gu, W., Ericsson, D.J., Foley, G., Hughes, R.O., Bosanac, T., von Itzstein, M., Rathjen, J.P., Nanson, J.D., Boden, M., Dry, I.B., Williams, S.J., Staskawicz, B.J., Coleman, M.P., Ve, T., Dodds, P.N. and Kobe, B. NAD(+) cleavage activity by animal and plant TIR domains in cell death pathways. Science 365 (2019) 793-799. [PMID: 31439792]
2. Wan, L., Essuman, K., Anderson, R.G., Sasaki, Y., Monteiro, F., Chung, E.H., Osborne Nishimura, E., DiAntonio, A., Milbrandt, J., Dangl, J.L. and Nishimura, M.T. TIR domains of plant immune receptors are NAD(+)-cleaving enzymes that promote cell death. Science 365 (2019) 799-803. [PMID: 31439793]
3. Duxbury, Z., Wang, S., MacKenzie, C.I., Tenthorey, J.L., Zhang, X., Huh, S.U., Hu, L., Hill, L., Ngou, P.M., Ding, P., Chen, J., Ma, Y., Guo, H., Castel, B., Moschou, P.N., Bernoux, M., Dodds, P.N., Vance, R.E. and Jones, J.DG. Induced proximity of a TIR signaling domain on a plant-mammalian NLR chimera activates defense in plants. Proc. Natl. Acad. Sci. USA 117 (2020) 18832-18839. [PMID: 32709746]
4. Manik, M.K., Shi, Y., Li, S., Zaydman, M.A., Damaraju, N., Eastman, S., Smith, T.G., Gu, W., Masic, V., Mosaiab, T., Weagley, J.S., Hancock, S.J., Vasquez, E., Hartley-Tassell, L., Kargios, N., Maruta, N., Lim, B.YJ., Burdett, H., Landsberg, M.J., Schembri, M.A., Prokes, I., Song, L., Grant, M., DiAntonio, A., Nanson, J.D., Guo, M., Milbrandt, J., Ve, T. and Kobe, B. Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling. Science 377 (2022) eadc8969. [PMID: 36048923]
Accepted name: 3'-cyclic-ADP-D-ribose synthase
Reaction: NAD+ = (1''-3')-cyclic adenosine diphosphate-β-D-ribose + nicotinamide
Glossary: (1''-3')-cyclic adenosine diphosphate-β-D-ribose = 1''-3' glycocyclic ADP-β-D-ribose = (1''-3')-cyclic ADP-β-D-ribose = (1''-3')-cyclic ADP-ribose = 3'-cADPR = 1''-3' gcADPR = v2-cADPR
Other name(s): 3'cADPR synthase; v2-cADPR synthase; HopAM1; thsB (gene name)
Systematic name: NAD+ lyase [(1''-3')-cyclic adenosine diphosphate-β-D-ribose-forming]
Comments: The enzyme, found in bacteria, contains a TIR (Toll/interleukin-1 receptor) domain. Activity requires self-association into larger aggregates.The enzyme is part of the Thoeris system, which is responsible for antiphage defense. Its product, (1''-3')-cyclic adenosine diphosphate-β-D-ribose, activates EC 3.2.2.5, NAD+ glycohydrolase. In addition, as demonstrated with the plant pathogen Pseudomonas syringae, this compound suppresses the plant's immune system. cf. EC 4.3.99.6, 2'-cyclic-ADP-D-ribose synthase, and EC 3.2.2.6, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase.
References:
1. Eastman, S., Smith, T., Zaydman, M.A., Kim, P., Martinez, S., Damaraju, N., DiAntonio, A., Milbrandt, J., Clemente, T.E., Alfano, J.R. and Guo, M. A phytobacterial TIR domain effector manipulates NAD(+) to promote virulence. New Phytol. 233 (2022) 890-904. [PMID: 34657283]
2. Ofir, G., Herbst, E., Baroz, M., Cohen, D., Millman, A., Doron, S., Tal, N., Malheiro, D.BA., Malitsky, S., Amitai, G. and Sorek, R. Antiviral activity of bacterial TIR domains via immune signalling molecules. Nature 600 (2021) 116-120. [PMID: 34853457]
3. Manik, M.K., Shi, Y., Li, S., Zaydman, M.A., Damaraju, N., Eastman, S., Smith, T.G., Gu, W., Masic, V., Mosaiab, T., Weagley, J.S., Hancock, S.J., Vasquez, E., Hartley-Tassell, L., Kargios, N., Maruta, N., Lim, B.YJ., Burdett, H., Landsberg, M.J., Schembri, M.A., Prokes, I., Song, L., Grant, M., DiAntonio, A., Nanson, J.D., Guo, M., Milbrandt, J., Ve, T. and Kobe, B. Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling. Science 377 (2022) eadc8969. [PMID: 36048923]
Accepted name: 6-(L-cystein-S-yl)-6-deoxy-5'-guanylate lyase
Reaction: 6-(L-cystein-S-yl)-6-deoxy-5'-guanylate + H2O = 6-thio-5'-guanylate + pyruvate + ammonium (overall reaction)
(1a) 6-(L-cystein-S-yl)-6-deoxy-5'-guanylate = 6-thio-5'-guanylate + 2-aminoprop-2-enoate
(1b) 2-aminoprop-2-enoate = 2-iminopropanoate (spontaneous)
(1c) 2-iminopropanoate + H2O = pyruvate + ammonium (spontaneous)
Other name(s): ycfC (gene name); 6-(S-L-cysteinyl)-GMP lyase
Systematic name: 6-(L-cystein-S-yl)-6-deoxy-5'-guanylate 6-thio-5'-guanylate-lyase (deaminating; pyruvate-forming)
Comments: A pyridoxal 5'-phosphate protein. The enzyme, characterized from the plant pathogen Erwinia amylovora, is involved in production of 6-thioguanine, a virulence factor involved in the fire blight disease, which infects apples and pears. The enzyme cleaves a carbon-sulfur bond, likely releasing a thiol and an unstable enamine product that tautomerizes to an imine form, which undergoes a hydrolytic deamination to form pyruvate and ammonia.
References:
1. Litomska, A., Ishida, K., Dunbar, K.L., Boettger, M., Coyne, S. and Hertweck, C. Enzymatic thioamide formation in a bacterial antimetabolite pathway. Angew. Chem. Int. Ed. Engl. 57 (2018) 11574-11578. [PMID: 29947149]
2. Ishida, K., Litomska, A., Dunbar, K.L. and Hertweck, C. An enzymatic prodrug-like route to thio and selenoamides. Angew. Chem. Int. Ed. Engl. 63 (2024) e202404243. [PMID: 38747847]
Accepted name: cysteate racemase
Reaction: L-cysteate = D-cysteate
Other name(s): cuyB (gene name); cysteic acid racemase
Systematic name: cysteate racemase
Comments: The enzyme, characterized from the bacteria Bilophila wadsworthia and Ruegeria pomeroyi, participates in L-cysteate degradation.
References:
1. Burchill, L., Stewart, A.WE., Pallasdies, L., Lee, M., Coe, L.SY., Zudich, L., Jebeli, L., Sharma, M., Hofferek, V., McConville, M.J., Davies, G.J., Scott, N.E., Durham, B.P. and Williams, S.J. Bridging a gap in marine sulfur cycling: discovery of a D-cysteinolic acid degradation pathway. J. Am. Chem. Soc. 147 (2025) 47934-47941. [PMID: 41404639]
2. Liu, C., Ma, K., Jiang, L., Liu, X., Tong, Y., Yang, S., Jin, X., Wei, Y. and Zhang, Y. Bacterial cysteate dissimilatory pathway involves a racemase and D-cysteate sulfo-lyase. J. Biol. Chem. 300 (2024) 107371. [PMID: 38750791]
Accepted name: cysteinolate racemase
Reaction: D-cysteinolate = L-cysteinolate
Glossary: cysteinolate = 2-amino-3-hydroxypropane-1-sulfonate
D-cysteinolate = (2S)-2-amino-3-hydroxypropane-1-sulfonate
L-cysteinolate = (2R)-2-amino-3-hydroxypropane-1-sulfonate
Other name(s): claA (gene name); cuyC (gene name); cysteinolic acid racemase
Systematic name: cysteinolate racemase
Comments: A pyridoxal-phosphate dependent protein. This enzyme, characterized from the bacteria Ruegeria pomeroyi and Bilophila sp. 4_1_30, participates in a D-cysteinolate degradation pathway.
References:
1. Burchill, L., Stewart, A.WE., Pallasdies, L., Lee, M., Coe, L.SY., Zudich, L., Jebeli, L., Sharma, M., Hofferek, V., McConville, M.J., Davies, G.J., Scott, N.E., Durham, B.P. and Williams, S.J. Bridging a gap in marine sulfur cycling: discovery of a D-cysteinolic acid degradation pathway. J. Am. Chem. Soc. 147 (2025) 47934-47941. [PMID: 41404639]
2. Liu, X., Hu, Y., An, J., Zhang, C., Tan, J., Wei, Y. and Zhang, Y. A pathway for D-cysteinolate degradation in sulfate- and sulfite-reducing bacteria. J. Biol. Chem. 302 (2026) 111055. [PMID: 41391761]
Accepted name: 2-amino-1-hydroxyethylphosphonate racemase
Reaction: (1S)-(2-amino-1-hydroxyethyl)phosphonate = (1R)-(2-amino-1-hydroxyethyl)phosphonate
Other name(s): 1-hydroxy-2-aminoethylphosphonate racemase; HAEP racemase; pbfF (gene name)
Systematic name: 2-amino-1-hydroxyethylphosphonate racemase
Comments: The enzyme, characterized from the bacterium Mesorhizobium plurifarium, contains an NAD+ cofactor that is reduced transiently during the reaction.
References:
1. Ruffolo, F., Conciatori, S., Merici, G., Dinhof, T., Chin, J.P., Rivetti, C., Secchi, A., Pallitsch, K. and Peracchi, A. Genomic context analysis enables the discovery of an unusual NAD-dependent racemase in phosphonate catabolism. FEBS J. 292 (2025) 4272-4288. [PMID: 40384479]
Accepted name: N-acyl-2-dehydroaromatic-amino-acid cyclase
Reaction: (1) ATP + a (2E)-N-acyl-2-dehydrotryptophan = AMP + diphosphate + an alkyltryptazolone
(2) ATP + a (2E)-N-acyl-2-dehydrotyrosine = AMP + diphosphate + an alkyltyrazolone
(3) ATP + a (2E)-N-acyl-2-dehydrophenylalanine = AMP + diphosphate + an alkylphenazolone;
Glossary: an alkyltryptazolone = a (4E)-2-alkyl-4-(1H-indol-3-ylmethylidene)-1,3-oxazol-5-one
an alkyltyrazolone = a (4E)-4-[(4-hydroxyphenyl)methylidene]-2-alkyl-1,3-oxazol-5-one
an alkylphenazolone = a (4E)-4-(phenylmethylidene)-2-alkyl-1,3-oxazol-5-one
Other name(s): tyzB (gene name); oxzB (gene name); trzS (gene name)
Systematic name: (2E)-N-acyl-2-dehydroaromatic amino acid cyclase (oxazolone-forming)
Comments: The enzyme, found in Gram-negative and Gram-positive bacteria, has sequence similarity to EC 2.7.7.73, sulfur carrier protein ThiS adenylyltransferase. The enzyme uses ATP to activate the carboxylate moiety of its substrate, resulting in dehydration and formation of an oxazolone ring. The enzyme acts along EC 1.3.3.19, N-acyl-aromatic-amino-acid desaturase, and the order in which the two enzymes act has not been determined conclusively. In some organisms the two enzymes form a fusion protein.
References:
1. de Rond, T., Asay, J.E. and Moore, B.S. Co-occurrence of enzyme domains guides the discovery of an oxazolone synthetase. Nat. Chem. Biol. 17 (2021) 794-799. [PMID: 34099916]
2. Grigg, J.C., Copp, J.N., Krekhno, J.MC., Liu, J., Ibrahimova, A. and Eltis, L.D. Deciphering the biosynthesis of a novel lipid in Mycobacterium tuberculosis expands the known roles of the nitroreductase superfamily. J. Biol. Chem. 299 (2023) 104924. [PMID: 37328106]
3. Kleetz, J., Grigg, J.C., Hassan, A.A., Ibtisam, A., Copp, J.N., Lian, J., Liu, J. and Eltis, L.D. The biosynthesis of N-acylated tryptazolone in Mycobacterium tuberculosis and related bacteria. J. Biol. Chem. 302 (2026) 111079. [PMID: 41429352]
EC 6.2.2.4 Accepted name: guanine nucleotide—L-cysteine ligase
Reaction: ATP + GMP + L-cysteine = 6-(L-cystein-S-yl)-6-deoxy-5'-guanylate + AMP + diphosphate (overall reactions)
(1a) ATP + GMP = 6-(adenylyl)-5'-guanylate + diphosphate
(1b) 6-(adenylyl)-5'-guanylate + L-cysteine = 6-(L-cystein-S-yl)-6-deoxy-5'-guanylate + AMP
Other name(s): ycfA (gene name)
Systematic name: guanine nucleotide—L-cysteine ligase [6-(L-cysteinyl-S)-guanine nucleotide-forming]
Comments: The enzyme, characterized from the plant pathogen Erwinia amylovora, is involved in production of 6-thioguanine, a virulence factor involved in the fire blight disease, which infects apples and pears. While the reaction shown uses GMP, the enzyme can also act on GDP and GTP.
References:
1. Coyne, S., Chizzali, C., Khalil, M.N., Litomska, A., Richter, K., Beerhues, L. and Hertweck, C. Biosynthesis of the antimetabolite 6-thioguanine in Erwinia amylovora plays a key role in fire blight pathogenesis. Angew. Chem. Int. Ed. Engl. 52 (2013) 10564-10568. [PMID: 24038828]
2. Litomska, A., Ishida, K., Dunbar, K.L., Boettger, M., Coyne, S. and Hertweck, C. Enzymatic thioamide formation in a bacterial antimetabolite pathway. Angew. Chem. Int. Ed. Engl. 57 (2018) 11574-11578. [PMID: 29947149]
3. Ishida, K., Litomska, A., Dunbar, K.L. and Hertweck, C. An enzymatic prodrug-like route to thio and selenoamides. Angew. Chem. Int. Ed. Engl. 63 (2024) e202404243. [PMID: 38747847]
Accepted name: succinate dehydrogenase (electrogenic, proton-motive force generating)
Reaction: succinate + a quinone + 2 H+[side 1] = fumarate + a quinol + 2 H+[side 2]
Systematic name: succinate:quinone oxidoreductase (electrogenic, proton-motive force generating)
Comments: The enzyme is very similar to EC 1.3.5.1, succinate dehydrogenase, but differs by containing two heme molecules (located in the membrane anchor component) in addition to FAD and three iron-sulfur clusters. Unlike EC 1.3.5.1, this enzyme catalyses an electrogenic reaction, enabled by electron-bifurcation via the heme molecules. In the direction of succinate oxidation by quinone, which is endergonic, the reaction is driven by the transmembrane electrochemical proton potential. In the direction of fumarate reduction, the electrogenic electron transfer reaction is compensated by transmembrane proton transfer pathway known as the E-pathway, which results in overall electroneutrality.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Lancaster, C.R. Wolinella succinogenes quinol:fumarate reductase-2.2-Å resolution crystal structure and the E-pathway hypothesis of coupled transmembrane proton and electron transfer. Biochim. Biophys. Acta 1565 (2002) 215-231. [PMID: 12409197]
2. Madej, M.G., Nasiri, H.R., Hilgendorff, N.S., Schwalbe, H., Unden, G. and Lancaster, C.R. Experimental evidence for proton motive force-dependent catalysis by the diheme-containing succinate:menaquinone oxidoreductase from the Gram-positive bacterium Bacillus licheniformis. Biochemistry 45 (2006) 15049-15055. [PMID: 17154542]
3. Lancaster, C.R., Herzog, E., Juhnke, H.D., Madej, M.G., Muller, F.G., Paul, R. and Schleidt, P.G. Electroneutral and electrogenic catalysis by dihaem-containing succinate:quinone oxidoreductases. Biochem Soc Trans. 36 (2008) 996-1000. [PMID: 18793177]
4. Lancaster, C.R. The di-heme family of respiratory complex II enzymes. Biochim. Biophys Acta 1827 (2013) 679-687. [PMID: 23466335]
5. Guan, H.H., Hsieh, Y.C., Lin, P.J., Huang, Y.C., Yoshimura, M., Chen, L.Y., Chen, S.K., Chuankhayan, P., Lin, C.C., Chen, N.C., Nakagawa, A., Chan, S.I. and Chen, C.J. Structural insights into the electron/proton transfer pathways in the quinol:fumarate reductase from Desulfovibrio gigas. Sci. Rep. 8 (2018) 14935. [PMID: 30297797]