An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: (S)-malate dehydrogenase (NAD+, oxaloacetate-forming)
Reaction: (S)-malate + NAD+ = oxaloacetate + NADH + H+
For diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here, for diagram of the citric acid cycle, click here and for diagram of the glyoxylate cycle, click here
Other name(s): malic dehydrogenase (ambiguous); L-malate dehydrogenase (ambiguous); NAD-L-malate dehydrogenase (ambiguous); malic acid dehydrogenase (ambiguous); NAD-dependent malic dehydrogenase (ambiguous); NAD-malate dehydrogenase (ambiguous); NAD-malic dehydrogenase (ambiguous); malate (NAD) dehydrogenase (ambiguous); NAD-dependent malate dehydrogenase (ambiguous); NAD-specific malate dehydrogenase (ambiguous); NAD-linked malate dehydrogenase (ambiguous); MDH (ambiguous); L-malate-NAD+ oxidoreductase (ambiguous); malate dehydrogenase (ambiguous); aromatic α-keto acid; KAR; 2-oxo acid reductase
Systematic name: (S)-malate:NAD+ oxidoreductase
Comments: There are several forms of malate dehydrogenases that differ in their use of substrates and cofactors. This NAD+-dependent enzyme forms oxaloacetate and unlike EC 1.1.1.38, malate dehydrogenase (oxaloacetate-decarboxylating), is unable to convert it to pyruvate. Also oxidizes some other 2-hydroxydicarboxylic acids and aromatic α-keto acids. cf. EC 1.1.1.82, malate dehydrogenase (NADP+), EC 1.1.1.299, malate dehydrogenase [NAD(P)+] and EC 1.1.5.4, malate dehydrogenase (quinone).
Links to other databases: BRENDA, EXPASY, GENE, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9001-64-3
References:
1. Wolfe, R.G. and Nielands, J.B. Some molecular and kinetic properties of heart malic dehydrogenase. J. Biol. Chem. 221 (1956) 61-69. [PMID: 13345798]
2. Guha, A., Englard, S. and Listowsky, I. Beef heart malic dehydrogenases. VII. Reactivity of sulfhydryl groups and conformation of the supernatant enzyme. J. Biol. Chem. 243 (1968) 609-615. [PMID: 5637713]
3. McReynolds, M.S. and Kitto, G.B. Purification and properties of Drosophila malate dehydrogenases. Biochim. Biophys. Acta 198 (1970) 165-175. [PMID: 4313528]
4. Banaszak, L.J. and Bradshaw, R.A. Malate dehydrogenase. In: Boyer, P.D. (Ed.), The Enzymes, 3rd edn, vol. 11, Academic Press, New York, 1975, pp. 369-396.
5. Friedrich, C.A., Morizot, D.C., Siciliano, M.J. and Ferrell, R.E. The reduction of aromatic α-keto acids by cytoplasmic malate dehydrogenase and lactate dehydrogenase. Biochem. Genet. 25 (1987) 657-669. [PMID: 2449162]
6. Friedrich, C.A., Ferrell, R.E., Siciliano, M.J. and Kitto, G.B. Biochemical and genetic identity of α-keto acid reductase and cytoplasmic malate dehydrogenase from human erythrocytes. Ann. Hum. Genet. 52 (1988) 25-37. [PMID: 3052244]
[EC 1.1.1.96 Transferred entry: diiodophenylpyruvate reductase. The enzyme is identical to EC 1.1.1.37, (S)-malate dehydrogenase (NAD+, oxaloacetate-forming) (EC 1.1.1.96 created 1972, deleted 2025)]
Accepted name: 20β-hydroxysteroid dehydrogenase
Reaction: 20β-dihydrocortisol + NAD+ = cortisol + NADH + H+
Other name(s): 20β-HSDH; desE (gene name)
Systematic name: 20β-dihydrocortisol:NAD+ 20-oxidoreductase
Comments: The enzyme, characterized from several gut bacteria, is specific for NADH and is much more active in the reductive direction. cf. the eukaryotic enzyme EC 1.1.1.53, 3α(or 20β)-hydroxysteroid dehydrogenase.
References:
1. Devendran, S., Mendez-Garcia, C. and Ridlon, J.M. Identification and characterization of a 20β-HSDH from the anaerobic gut bacterium Butyricicoccus desmolans ATCC 43058. J. Lipid Res. 58 (2017) 916-925. [PMID: 28314858]
2. Doden, H.L., Pollet, R.M., Mythen, S.M., Wawrzak, Z., Devendran, S., Cann, I., Koropatkin, N.M. and Ridlon, J.M. Structural and biochemical characterization of 20β-hydroxysteroid dehydrogenase from Bifidobacterium adolescentis strain L2-32. J. Biol. Chem. 294 (2019) 12040-12053. [PMID: 31209107]
Accepted name: questin reductase
Reaction: questin hydroquinone + NADP+ = questin + NADPH + H+
Glossary: questin = 1,6-dihydroxy-8-methoxy-3-methylanthracene-9,10-dione
Other name(s): gedF (gene name)
Systematic name: questin hydroquinone:NADP+ 10-oxidoreductase
Comments: The enzyme, characterized from the fungus Aspergillus terreus, catalyses a step in the biosynthesis of (+)-geodin.
References:
1. Qi, F., Zhang, W., Xue, Y., Geng, C., Huang, X., Sun, J. and Lu, X. Bienzyme-catalytic and dioxygenation-mediated anthraquinone ring opening. J. Am. Chem. Soc. 143 (2021) 16326-16331. [PMID: 34586791]
Accepted name: sulfofucose 1-dehydrogenase
Reaction: sulfofucose + NAD+ = 6-deoxy-6-sulfo-D-galactono-1,5-lactone + NADH + H+
Glossary: sulfofucose = 6-deoxy-6-sulfo-D-galactopyranose
Other name(s): sulfofucose dehydrogenase; SfcH
Systematic name: 6-deoxy-6-sulfo-D-galactopyranose:NAD+ 1-oxidoreductase
Comments: This enzyme, characterized from the bacterium Paracoccus wurundjeri strain Merri, participates in a sulfofucose degradation pathway. Activity with NADP+ is 28% of that with NAD+. cf. EC 1.1.1.390, sulfoquinovose 1-dehydrogenase.
References:
1. Stewart, A.WE., Li, J., Lee, M., Lewis, J.M., Herisse, M., Hofferek, V., McConville, M.J., Pidot, S.J., Scott, N.E. and Williams, S.J. Tandem sulfofucolytic-sulfolactate sulfolyase pathway for catabolism of the rare sulfosugar sulfofucose. mBio 16 (2025) e0184025. [PMID: 40823846]
[EC 1.2.1.52 Deleted entry: oxoglutarate dehydrogenase (NADP+). The reaction described does not exist. (EC 1.2.1.52 created 1989, deleted 2025)]
Accepted name: pyruvate synthase (ferredoxin)
Reaction: pyruvate + CoA + 2 oxidized ferredoxin = acetyl-CoA + CO2 + 2 reduced ferredoxin + 2 H+
For diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here
Other name(s): pyruvate oxidoreductase (ambiguous); pyruvate synthetase (ambiguous); pyruvate:ferredoxin oxidoreductase; pyruvic-ferredoxin oxidoreductase; 2-oxobutyrate synthase; α-ketobutyrate-ferredoxin oxidoreductase; 2-ketobutyrate synthase; α-ketobutyrate synthase; 2-oxobutyrate-ferredoxin oxidoreductase; 2-oxobutanoate:ferredoxin 2-oxidoreductase (CoA-propionylating); 2-oxobutanoate:ferredoxin 2-oxidoreductase (CoA-propanoylating); pyruvate synthase
Systematic name: pyruvate:ferredoxin 2-oxidoreductase (CoA-acetylating)
Comments: Contains thiamine diphosphate and [4Fe-4S] clusters. The enzyme, common in bacteria, archaea, and some algae, catalyses the reversible decarboxylation of pyruvate with the formation of acetyl-CoA. Enzymes from different organisms catalyse the reaction in different directions depending on their metabolic needs. The enzyme also decarboxylates 2-oxobutanoate with lower efficiency, but shows no activity with 2-oxoglutarate. In some organisms ferredoxin may be replaced by the flavin mononucleotide (FMN)-containing flavodoxin under conditions of low iron and high oxygen (cf. EC 1.2.8.1, pyruvate synthase (flavodoxin)). This enzyme is a member of the 2-oxoacid oxidoreductases, a family of enzymes that oxidatively decarboxylate different 2-oxoacids to form their CoA derivatives, and are differentiated based on their substrate specificity. For examples of other members of this family, see EC 1.2.7.3, 2-oxoglutarate synthase and EC 1.2.7.7, 3-methyl-2-oxobutanoate dehydrogenase (ferredoxin).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9082-51-3
References:
1. Evans, M.C.W. and Buchanan, B.B. Photoreduction of ferredoxin and its use in carbon dioxide fixation by a subcellular system from a photosynthetic bacterium. Proc. Natl. Acad. Sci. USA 53 (1965) 1420-1425. [PMID: 5217644]
2. Gehring, U. and Arnon, D.I. Purification and properties of α-ketoglutarate synthase from a photosynthetic bacterium. J. Biol. Chem. 247 (1972) 6963-6969. [PMID: 4628267]
3. Uyeda, K. and Rabinowitz, J.C. Pyruvate-ferredoxin oxidoreductase. 3. Purification and properties of the enzyme. J. Biol. Chem. 246 (1971) 3111-3119. [PMID: 5574389]
4. Uyeda, K. and Rabinowitz, J.C. Pyruvate-ferredoxin oxidoreductase. IV. Studies on the reaction mechanism. J. Biol. Chem. 246 (1971) 3120-3125. [PMID: 4324891]
5. Charon, M.-H., Volbeda, A., Chabriere, E., Pieulle, L. and Fontecilla-Camps, J.C. Structure and electron transfer mechanism of pyruvate:ferredoxin oxidoreductase. Curr. Opin. Struct. Biol. 9 (1999) 663-669. [PMID: 10607667]
6. Cossu, M., Catlin, D., Elliott, S.J., Metcalf, W.W. and Nair, S.K. Structural organization of pyruvate: ferredoxin oxidoreductase from the methanogenic archaeon Methanosarcina acetivorans, Structure 32 (2024) 1963-1972.e3. [PMID: 39265575]
7. Yakunin, A.F. and Hallenbeck, P.C. Purification and characterization of pyruvate oxidoreductase from the photosynthetic bacterium Rhodobacter capsulatus, Biochim. Biophys Acta 1409 (1998) 39-49. [PMID: 9804883]
EC 1.2 Acting on the aldehyde or oxo group of donors
EC 1.2.8 With a flavin or flavoprotein as acceptor
Accepted name: pyruvate synthase (flavodoxin)
Reaction: pyruvate + CoA + flavodoxin = acetyl-CoA + CO2 + reduced flavodoxin
Other name(s): pyruvate oxidoreductase (ambiguous); pyruvate synthetase (ambiguous); pyruvate:flavodoxin oxidoreductase; pyruvic-flavodoxin oxidoreductase
Systematic name: pyruvate:flavodoxin 2-oxidoreductase (CoA-acetylating)
Comments: The enzyme, found in some bacteria, uses the flavin mononucleotide (FMN)-containing protein flavodoxin as an electron donor under high-oxygen and low iron conditions. In some organisms ferredoxin may replace flavodoxin [cf. EC 1.2.7.1, pyruvate synthase (ferredoxin)]. The reaction is freely reversible. Reduced flavodoxin formed by the enzyme can serve as an electron donor for several enzymes, such as EC 1.19.6.1, nitrogenase (flavodoxin).
References:
1. Shah, V.K., Stacey, G. and Brill, W.J. Electron transport to nitrogenase. Purification and characterization of pyruvate:flavodoxin oxidoreductase. The nifJ gene product. J. Biol. Chem. 258 (1983) 12064-12068. [PMID: 6352705]
2. Hughes, N.J., Clayton, C.L., Chalk, P.A. and Kelly, D.J. Helicobacter pylori porCDAB and oorDABC genes encode distinct pyruvate:flavodoxin and 2-oxoglutarate:acceptor oxidoreductases which mediate electron transport to NADP. J. Bacteriol. 180 (1998) 1119-1128. [PMID: 9495749]
3. Nakayama, T., Yonekura, S., Yonei, S. and Zhang-Akiyama, Q.M. Escherichia coli pyruvate:flavodoxin oxidoreductase, YdbK - regulation of expression and biological roles in protection against oxidative stress. Genes Genet. Syst. 88 (2013) 175-188. [PMID: 24025246]
4. Blaschkowski, H.P., Neuer, G., Ludwig-Festl, M. and Knappe, J. Routes of flavodoxin and ferredoxin reduction in Escherichia coli. CoA-acylating pyruvate: flavodoxin and NADPH: flavodoxin oxidoreductases participating in the activation of pyruvate formate-lyase. Eur. J. Biochem. 123 (1982) 563-569. [PMID: 7042345]
Accepted name: (2E)-2-enoyl-CoA carboxylase/reductase
Reaction: a 2-carboxyacyl-CoA + NADP+ = a (2E)-2-enoyl-CoA + CO2 + NADPH + H+
Glossary: 2-carboxyacyl-CoA = 2-alkylmalonyl-CoA
Other name(s): divR (gene name); antE (gene name); revT (gene name); salG (gene name)
Systematic name: 2-carboxyacyl-CoA:NADP+ oxidoreductase (decarboxylating)
Comments: This bacterial enzyme, which is similar to EC 1.3.1.85, crotonyl-CoA carboxylase/reductase, has a broad substrate range and participates in production of different 2-carboxyacyl-CoA products, which serve as unusual extender units for some polyketide synthases. The enzyme belongs to the medium-chain reductase/dehydrogenase (MDR) superfamily and requires an NADPH cosubstrate. The carboxylation reaction mechanism begins with the transfer of the hydride from NADPH onto the β-carbon of the enoyl-CoA to yield a thioester enolate, followed by the electrophilic attack of CO2 at the α-carbon.
References:
1. Liu, Y., Hazzard, C., Eustaquio, A.S., Reynolds, K.A. and Moore, B.S. Biosynthesis of salinosporamides from α,β-unsaturated fatty acids: implications for extending polyketide synthase diversity. J. Am. Chem. Soc. 131 (2009) 10376-10377. [PMID: 19601645]
2. Xu, Z., Ding, L. and Hertweck, C. A branched extender unit shared between two orthogonal polyketide pathways in an endophyte. Angew. Chem. Int. Ed. Engl. 50 (2011) 4667-4670. [PMID: 21506215]
3. Sandy, M., Rui, Z., Gallagher, J. and Zhang, W. Enzymatic synthesis of dilactone scaffold of antimycins. ACS Chem. Biol. 7 (2012) 1956-1961. [PMID: 22971101]
4. Miyazawa, T., Takahashi, S., Kawata, A., Panthee, S., Hayashi, T., Shimizu, T., Nogawa, T. and Osada, H. Identification of middle chain fatty acyl-CoA ligase responsible for the biosynthesis of 2-alkylmalonyl-CoAs for polyketide extender unit. J. Biol. Chem. 290 (2015) 26994-27011. [PMID: 26378232]
EC 1.3.3.18
Accepted name: 5-bromoskatole synthase
Reaction: 5-bromo-L-tryptophan + O2 = 5-bromoskatole + cyanide + CO2 + H2O2
Glossary: 5-bromoskatole = 5-bromo-3-methyl-1H-indole
Other name(s): SktA; skatole synthase
Systematic name: 5-bromo-L-tryptophan:oxygen oxidoreductase (5-bromoskatole forming)
Comments: The enzyme, isolated from the cyanobacterium Nostoc punctiforme, requires Fe(II). It is an oxygen-dependent diiron oxidase. The C-2 hydrogen of tryptophan is transferred in the reaction to the methyl group of skatole. The enzyme also acts on L-tryptophan, forming skatole.
References:
1. Adak, S., Calderone, L.A., Krueger, A., Pandelia, M.E. and Moore, B.S. Single-enzyme conversion of tryptophan to skatole and cyanide expands the mechanistic competence of diiron oxidases. J. Am. Chem. Soc. 147 (2025) 6326-6331. [PMID: 39939147]
Accepted name: iminosuccinate reductase
Reaction: L-aspartate + NAD+ = 2-iminosuccinate + NADH + H+
Other name(s): bhcD (gene name)
Systematic name: L-aspartate:NAD+ oxidoreductase (iminosuccinate-forming)
Comments: The enzyme, characterized from the bacterium Paracoccus denitrificans, participates in the the β-hydroxyaspartate cycle of glyoxylate assimilation. The substrate, 2-iminosuccinate, is very unstable, and spontaneously decays into free ammonia and oxaloacetate in the absence of the enzyme. cf. EC 1.4.1.21, aspartate dehydrogenase, which acts in the opposite direction, producing 2-iminosuccinate that transforms into ammonia and oxaloacetate.
References:
1. Schada von Borzyskowski, L., Severi, F., Kruger, K., Hermann, L., Gilardet, A., Sippel, F., Pommerenke, B., Claus, P., Cortina, N.S., Glatter, T., Zauner, S., Zarzycki, J., Fuchs, B.M., Bremer, E., Maier, U.G., Amann, R.I. and Erb, T.J. Marine Proteobacteria metabolize glycolate via the β-hydroxyaspartate cycle. Nature 575 (2019) 500-504. [PMID: 31723261]
Accepted name: torosachrysone 7,1'-coupling laccase
Reaction: 4 (R)-torosachrysone + O2 = 2 phlegmacin + 2 H2O
Other name(s): phlC (gene name)
Systematic name: (R)-torosachrysone:oxygen oxidoreductase (phlegmacin-forming)
Comments: The enzyme, characterized from the ascomycete fungus Talaromyces sp. F08Z-0631, catalyses the regioselective coupling of two molecules of the phenolic compound (R)-torosachrysone at the corresponding C7 and C10' positions, forming the 7,1'-coupled dimeric product (phlegmacin). The reaction requires the participation of a fasciclin partner protein. cf. EC 1.11.2.7, torosachrysone 7,1'-coupling peroxygenase.
References:
1. Zhao, Q., Zhuang, Z., Liu, T., Yang, Q., He, Q.L., Liu, W. and Lin, G.Q. Unsymmetrically regioselective homodimerization depends on the subcellular colocalization of laccase/fasciclin protein in the biosynthesis of phlegmacins. ACS Chem. Biol. 17 (2022) 791-796. [PMID: 35274920]
2. Platz, L., Lohr, N.A., Girkens, M.P., Eisen, F., Braun, K., Fessner, N., Bar, C., Huttel, W., Hoffmeister, D. and Muller, M. Regioselective oxidative phenol coupling by a mushroom unspecific peroxygenase. Angew. Chem. Int. Ed. Engl. 63 (2024) e202407425. [PMID: 38963262]
Accepted name: questin hydroquinone dioxygenase
Reaction: questin hydroquinone + O2 = demethylsulochrin
Glossary: questin hydroquinone = 1,6,10-trihydroxy-8-methoxy-3-methyl-10H-anthracen-9-one
demethylsulochrin = 2-(2,6-dihydroxy-4-methylbenzoyl)-5-hydroxy-3-methoxybenzoate
Other name(s): gedK (gene name)
Systematic name: questin hydroquinone:oxygen 10,4a-oxidoreductase (ring-opening)
Comments: The enzyme, characterized from the fungus Aspergillus terreus, cleaves the C-10—C-4a bond of the anthraquinone ring during the biosynthesis of (+)-geodin.
References:
1. Qi, F., Zhang, W., Xue, Y., Geng, C., Huang, X., Sun, J. and Lu, X. Bienzyme-catalytic and dioxygenation-mediated anthraquinone ring opening. J. Am. Chem. Soc. 143 (2021) 16326-16331. [PMID: 34586791]
[EC 1.14.13.43 Transferred entry: questin monooxygenase. This activity was shown to be catalyzed by EC 1.1.1.443, questin reductase, and EC 1.13.11.96, questin hydroquinone dioxygenase. (EC 1.14.13.43 created 1992, deleted 2025)]
Accepted name: polyporic acid monooxygenase
Reaction: polyporic acid + [reduced NADPH—hemoprotein reductase] + O2 = ascocorynin + [oxidized NADPH—hemoprotein reductase] + H2O
Glossary: ascocorynin = 4-hydroxy-2-(4-hydroxyphenyl)-3,6-dioxo-5-phenylcyclohexa-1,4-dien-1-olate
Systematic name: polyporic acid,NADPH—hemoprotein reductase:oxygen oxidoreductase (ascocorynin-forming)
Comments: A cytochrome P-450 (heme-thiolate) enzyme. The enzyme has been characterized from the ascomycete fungus Ascocoryne sarcoides (purple jellydisc fungus). The product, ascocorynin, gives the fruiting body of this fungus a pink to purple color, which led to its common name.
References:
1. Wieder, C., Peres da Silva, R., Witts, J., Jager, C.M., Geib, E. and Brock, M. Characterisation of ascocorynin biosynthesis in the purple jellydisc fungus Ascocoryne sarcoides, Fungal Biol Biotechnol 9 (2022) 8. [PMID: 35477441]
Accepted name: progesterone 11α-monooxygenase
Reaction: progesterone + [reduced NADPH—hemoprotein reductase] + O2 = 11α-hydroxyprogesterone + [oxidized NADPH—hemoprotein reductase] + H2O
Other name(s): progesterone 11α-hydroxylase; CYP509C12 (gene name); CYP68L1 (gene name); CYP68L8 (gene name)
Systematic name: progesterone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (11α-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) enzyme. The enzyme, isolated from fungi, can hydroxylate testosterone, androst-4-ene-3,17-dione, and 11-deoxycorticosterone, forming the respective 11α-hydroxy compounds (cf. EC 1.14.15.4, steroid 11β-monooxygenase). The CYP509C12 enzyme from Rhizopus arrhizus can also 6-hydroxylate testosterone and 11-deoxycorticosterone, forming the respective β-hydroxy compounds [2].
References:
1. Shibahara, M., Moody, J.A. and Smith, L.L. Microbial hydroxylations. V. 11α-Hydroxylation of progesterone by cell-free preparations of Aspergillus ochraceus, Biochim. Biophys. Acta 202 (1970) 172-179. [PMID: 5417182]
2. Petric, S., Hakki, T., Bernhardt, R., Zigon, D. and Cresnar, B. Discovery of a steroid 11α-hydroxylase from Rhizopus oryzae and its biotechnological application. J. Biotechnol. 150 (2010) 428-437. [PMID: 20850485]
3. Ortega-de Los Rios, L., Getino, L., Galan, B., Garcia, J.L., Luengo, J.M., Chamizo-Ampudia, A. and Fernandez-Canon, J.M. Unlocking testosterone production by biotransformation: engineering a fungal model of Aspergillus nidulans strain deficient in steroid 11α-hydroxylase activity and expressing 17β-hydroxysteroid dehydrogenase enzyme as proof of concept. Biomolecules 14 (2024) 1502. [PMID: 39766209]
Accepted name: L-tyrosine 3-nitrase
Reaction: Met-Arg-Tyr-Leu-His + nitric oxide + O2 + reduced ferredoxin + H+ = Met-Arg-(3-NO2)-Tyr-Leu-His + H2O + oxidized ferredoxin
Glossary: (3-NO2)-Tyr = 3-nitro-L-tyrosine
Other name(s): rufO (gene name); 3-nitro-tyrosine synthase
Systematic name: Met-Arg-Tyr-Leu-His,nitric oxide, reduced ferredoxin:oxygen oxidoreductase (3-nitro-L-tyrosine-forming)
Comments: A cytochrome P-450 (heme-thiolate) enzyme characterized from the bacterium Streptomyces atratus. The enzyme participates in biosynthesis of rufomycins, circular heptapeptides with anti-mycobacterial activity. The enzyme requires ferredoxin as its electron donor and catalyses a reaction in which nitric oxide is oxidized to a nitro group and inserted into L-tyrosine present in the ribosomally-synthesized peptide Met-Arg-Tyr-Leu-His. The L-tyrosine is nitrosylated at the 3 position.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Tomita, H., Katsuyama, Y., Minami, H. and Ohnishi, Y. Identification and characterization of a bacterial cytochrome P450 monooxygenase catalyzing the 3-nitration of tyrosine in rufomycin biosynthesis. J. Biol. Chem. 292 (2017) 15859-15869. [PMID: 28774961]
2. Jordan, S., Li, B., Traore, E., Wu, Y., Usai, R., Liu, A., Xie, Z.R. and Wang, Y. Structural and spectroscopic characterization of RufO indicates a new biological role in rufomycin biosynthesis. J. Biol. Chem. 299 (2023) 105049. [PMID: 37451485]
3. Dratch, B.D., McWhorter, K.L., Blue, T.C., Jones, S.K., Horwitz, S.M. and Davis, K.M. Insights into substrate recognition by the unusual nitrating enzyme RufO. ACS Chem. Biol. 18 (2023) 1713-1718. [PMID: 37555759]
4. Padva, L., Zimmer, L., Gullick, J., Zhao, Y., Sasi, V.M., Schittenhelm, R.B., Jackson, C.J., Cryle, M.J. and Crüsemann, M. Ribosomal pentapeptide nitration for non-ribosomal peptide antibiotic precursor biosynthesis. Chem 11 (2025) 102438.
5. Nolan, K., Usai, R., Li, B., Jordan, S. and Wang, Y. Molecular basis for peptide nitration by a novel cytochrome P450 enzyme in RiPP biosynthesis. ACS Catal. 15 (2025) 10391-10404. [PMID: 40568218]
Accepted name: tryptophan 5-brominase (NADPH)
Reaction: L-tryptophan + NADPH + bromide + O2 + H+ = 5-bromo-L-tryptophan + NADP+ + 2 H2O
Other name(s): sktB (gene name); aetF (gene name)
Systematic name: L-tryptophan:NADPH oxidoreductase (5-brominating)
Comments: Contains FAD. The enzyme was isolated from the cyanobacteria Nostoc punctiforme and Aetokthonos hydrillicola. Unlike most other described tryptophan halogenases, the enzyme is self-sufficient and does not require a flavin reductase (single component halogenase). The enzyme from Aetokthonos hydrillicola also catalyses a second bromination reaction at the 7 position. cf. EC 1.14.19.58, tryptophan 5-halogenase.
References:
1. Breinlinger, S., Phillips, T.J., Haram, B.N., Mares, J., Martinez Yerena, J.A., Hrouzek, P., Sobotka, R., Henderson, W.M., Schmieder, P., Williams, S.M., Lauderdale, J.D., Wilde, H.D., Gerrin, W., Kust, A., Washington, J.W., Wagner, C., Geier, B., Liebeke, M., Enke, H., Niedermeyer, T.HJ. and Wilde, S.B. Hunting the eagle killer: A cyanobacterial neurotoxin causes vacuolar myelinopathy. Science 371 (2021) . [PMID: 33766860]
2. Adak, S., Lukowski, A.L., Schafer, R.JB. and Moore, B.S. From tryptophan to toxin: nature's convergent biosynthetic strategy to aetokthonotoxin. J. Am. Chem. Soc. 144 (2022) 2861-2866. [PMID: 35142504]
3. Gafe, S. and Niemann, H.H. Structural basis of regioselective tryptophan dibromination by the single-component flavin-dependent halogenase AetF. Acta Crystallogr D Struct Biol 79 (2023) 596-609. [PMID: 37314407]
4. Chen, C.C., Li, H., Huang, J.W. and Guo, R.T. Structural and molecular insights of two unique enzymes involved in the biosynthesis of a natural halogenated nitrile. FEBS J. 291 (2024) 5123-5132. [PMID: 39308083]
5. Adak, S., Calderone, L.A., Krueger, A., Pandelia, M.E. and Moore, B.S. Single-enzyme conversion of tryptophan to skatole and cyanide expands the mechanistic competence of diiron oxidases. J. Am. Chem. Soc. 147 (2025) 6326-6331. [PMID: 39939147]
[EC 1.14.99.14 Transferred entry: progesterone 11α-monooxygenase. Now EC 1.14.14.197, progesterone 11α-monooxygenase. (EC 1.14.99.14 created 1972, deleted 2025)]
Accepted name: phosphite dehydrogenase
Reaction: phosphite + NAD+ + H2O = phosphate + NADH + H+
Other name(s): NAD:phosphite oxidoreductase
Systematic name: phosphite:NAD+ oxidoreductase
Comments: The enzyme has been characterized from the bacterium Pseudomonas stutzeri WM88. NADP+ is a poor substitute for NAD+.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9031-35-0
References:
1. Costas, A.M.G., White, A.K. and Metcalf, W.W. Purification and characterization of a novel phosphorus-oxidizing enzyme from Pseudomonas stutzeri WM88. J. Biol. Chem. 276 (2001) 17429-17436. [PMID: 11278981]
2. Vrtis, J.M., White, A.K., Metcalf, W.W. and van der Donk, W.A. Phosphite dehydrogenase: An unusual phosphoryl transfer reaction. J. Am. Chem. Soc. 123 (2001) 2672-2673. [PMID: 11456941]
Accepted name: AMP-dependent phosphite dehydrogenase
Reaction: phosphite + AMP + NAD+ = ADP + NADH + H+
Other name(s): apdA (gene name)
Systematic name: phosphite:NAD+ oxidoreductase (ADP-forming)
Comments: The enzyme was characterized from the anaerobic bacteria Desulfotignum phosphitoxidans and Phosphitispora fastidiosa. Activity in vitro required the presence of EC 2.7.4.3, adenylate kinase. cf. EC 1.20.1.1, phosphite dehydrogenase.
References:
1. Mao, Z., Fleming, J.R., Mayans, O., Frey, J., Schleheck, D., Schink, B. and Muller, N. AMP-dependent phosphite dehydrogenase, a phosphorylating enzyme in dissimilatory phosphite oxidation. Proc. Natl. Acad. Sci. USA 120 (2023) e2309743120. [PMID: 37922328]
[EC 1.97.1.2 Transferred entry: pyrogallol hydroxytransferase, now classified as EC 5.4.4.9, pyrogallol hydroxytransferase. (EC 1.97.1.2 created 1992, deleted 2024)]
Accepted name: atrochrysone 6-O-methyltransferase
Reaction: S-adenosyl-L-methionine + (3R)-atrochrysone = S-adenosyl-L-homocysteine + (R)-torosachrysone
Glossary: (3R)-atrochrysone = (3R)-3,6,8,9-tetrahydroxy-3-methyl-3,4-dihydroanthracen-1(2H)-one
(R)-torosachrysone = (3R)-3,6,9-trihydroxy-6-methoxy-3-methyl-3,4-dihydroanthracen-1(2H)-one
Other name(s): CoOMT1
Systematic name: S-adenosyl-L-methionine:atrochrysone 6-O-methyltransferase
Comments: The enzyme was characterized from the mushroom Calonarius odorifer.
References:
1. Platz, L., Lohr, N.A., Girkens, M.P., Eisen, F., Braun, K., Fessner, N., Bar, C., Huttel, W., Hoffmeister, D. and Muller, M. Regioselective oxidative phenol coupling by a mushroom unspecific peroxygenase. Angew. Chem. Int. Ed. Engl. 63 (2024) e202407425. [PMID: 38963262]
Accepted name: 5-hydroxybenzimidazole ribotide O-methyltransferase
Reaction: S-adenosyl-L-methionine + 5-hydroxybenzimidazole ribotide = S-adenosyl-L-homocysteine + 5-methoxybenzimidazole ribotide
Glossary: 5-hydroxybenzimidazole ribotide = N1-(α-D-ribosyl)-5-hydroxybenzimidazole
5-methoxybenzimidazole ribotide = N1-(α-D-ribosyl)-5-methoxybenzimidazole
Other name(s): bzaC (gene name)
Systematic name: 5-hydroxybenzimidazole ribotide O-methyltransferase
Comments: The enzyme, characterized from the bacteria Eubacterium limosum and Moorella thermoacetica, participates in an anaerobic pathway for the biosynthesis the lower ligand used in cobalamin. Different species produce different lower ligands (i.e., 5-hydroxybenzimidazole, 5-methoxybenzimidazole, 5-methoxy-6-methylbenzimidazole, or 5,6-dimethylbenzimidazole).
References:
1. Hazra, A.B., Han, A.W., Mehta, A.P., Mok, K.C., Osadchiy, V., Begley, T.P. and Taga, M.E. Anaerobic biosynthesis of the lower ligand of vitamin B12. Proc. Natl. Acad. Sci. USA 112 (2015) 10792-10797. [PMID: 26246619]
2. Mathur, Y., Sreyas, S., Datar, P.M., Sathian, M.B. and Hazra, A.B. CobT and BzaC catalyze the regiospecific activation and methylation of the 5-hydroxybenzimidazole lower ligand in anaerobic cobamide biosynthesis. J. Biol. Chem. 295 (2020) 10522-10534. [PMID: 32503839]
Accepted name: sterol 4-C-methyltransferase
Reaction: 5α-cholest-7-en-3-one + S-adenosyl-L-methionine = 4α-methyl-5α-cholest-7-en-3-one + S-adenosyl-L-homocysteine
Glossary: lathosterone = 5α-cholest-7-en-3-one
lophenol = 4α-methyl-5α-cholest-7-en-3-one
Other name(s): 4-SMT; STRM-1
Systematic name: S-adenosyl-L-methionine:3-oxosterol 4-C-methyltransferase
Comments: The enzyme occurs in larvae of Caenorhabditis elegans. The reaction mechanism of C-4-methyl sterol formation is a two-step process of bound 3-oxo sterol undergoing active site isomerization to the 4-enol intermediate that is methylated by SAM in a stereoselective manner to yield the the equatorial 4α-methyl group, followed by rearrangement of the enol back to the 3-oxo form. The enzyme converts lathosterone to lophenol. Other substrates are cholest-4-en-3-one, cholest-5-en-3-one, and cholestanone.
References:
1. Hannich, J.T., Entchev, E.V., Mende, F., Boytchev, H., Martin, R., Zagoriy, V., Theumer, G., Riezman, I., Riezman, H., Knolker, H.J. and Kurzchalia, T.V. Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans, Dev. Cell 16 (2009) 833-843. [PMID: 19531354]
2. Zhou, W., Fisher, P.M., Vanderloop, B.H., Shen, Y., Shi, H., Maldonado, A.J., Leaver, D.J. and Nes, W.D. A nematode sterol C4α-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity. J. Lipid Res. 61 (2020) 192-204. [PMID: 31548366]
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
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: In the bacterium Bacillus subtilis it has been shown that the enzyme catalyses 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, 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. 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]
3. 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]
4. Cronan, J.E. Lipoic acid attachment to proteins: stimulating new developments. Microbiol. Mol. Biol. Rev. 88 (2024) e0000524. [PMID: 38624243]
Accepted name: 6-hydroxymusizin-2-carbonyl-[acyl-carrier protein] synthase
Reaction: [acyl-carrier protein] + 7 malonyl-CoA = 7 CoA + 6-hydroxymusizin-2-carbonyl-[acyl-carrier protein] + 7 CO2 + 2 H2O
Glossary: 6-hydroxymusizin = (1,6,8-trihydroxynaphthalen-2-yl)ethan-1-one
Other name(s): CrPKS1; CrPKS2; CrPKS3; CoPKS4
Systematic name: malonyl-CoA:malonyl-CoA malonyltransferase (6-hydroymusizin-2-carboxylate-forming)
Comments: The enzyme, a non-reducing iterative type I polyketide synthase, has been isolated from the mushrooms Calonarius odorifer and Calonarius rufo-olivaceus and the mould Chrysosporium merdarium. In some, but not all, cases the enzyme also contains a thioesterase domain and releases free 6-hydroxymusizin carboxylate (cf. EC 3.1.2.35, 6-hydroxymusizin-2-carbonyl-[acyl-carrier protein] thioesterase). Some of the enzymes also have the activity of EC 2.3.1.336, atrochrysone-2-carbonyl-[acyl-carrier protein] synthase.
References:
1. Thiele, W., Obermaier, S. and Muller, M. A fasciclin protein Is essential for laccase-mediated selective phenol coupling in sporandol biosynthesis. ACS Chem. Biol. 15 (2020) 844-848. [PMID: 32227858]
2. Lohr, N.A., Eisen, F., Thiele, W., Platz, L., Motter, J., Huttel, W., Gressler, M., Muller, M. and Hoffmeister, D. Unprecedented mushroom polyketide synthases produce the universal anthraquinone precursor. Angew. Chem. Int. Ed. Engl. 61 (2022) e202116142. [PMID: 35218274]
3. Lohr, N.A., Urban, M.C., Eisen, F., Platz, L., Huttel, W., Gressler, M., Muller, M. and Hoffmeister, D. The ketosynthase domain controls chain length in mushroom oligocyclic polyketide synthases. Chembiochem 24 (2023) e202200649. [PMID: 36507600]
4. Lohr, N.A., Rakhmanov, M., Wurlitzer, J.M., Lackner, G., Gressler, M. and Hoffmeister, D. Basidiomycete non-reducing polyketide synthases function independently of SAT domains. Fungal Biol Biotechnol 10 (2023) 17. [PMID: 37542286]
Accepted name: atrochrysone-2-carbonyl-[acyl-carrier protein] synthase
Reaction: [acyl-carrier protein] + 8 malonyl-CoA = (3R)-atrochrysone-2-carbonyl-[acyl-carrier protein] + 8 CO2 + 2 H2O + 8 CoA
Other name(s): CrPKS3; CoPKS4; TpcC; ACAS; ATEG_08451
Systematic name: malonyl-CoA:malonyl-CoA malonyltransferase [(R)-atrochrysone-carboxylate-forming]
Comments: The enzyme, a non-reducing iterative type I polyketide synthase, has been isolated from the moulds Aspergillus terreus and A. fumigatus and the mushrooms Calonarius odorifer and C. rufo-olivaceus. In some, but not all, cases the enzyme also contains a thioesterase domain and releases free atrochrysone-2-carboxylate (cf. EC 3.1.2.34 atrochrysone-2-carbonyl-[acyl-carrier protein] thioesterase). Some of the enzymes also have the activity of EC 2.3.1.335, 6-hydroxymusizin-2-carbonyl-[acyl-carrier protein] synthase.
References:
1. Askenazi, M., Driggers, E.M., Holtzman, D.A., Norman, T.C., Iverson, S., Zimmer, D.P., Boers, M.E., Blomquist, P.R., Martinez, E.J., Monreal, A.W., Feibelman, T.P., Mayorga, M.E., Maxon, M.E., Sykes, K., Tobin, J.V., Cordero, E., Salama, S.R., Trueheart, J., Royer, J.C. and Madden, K.T. Integrating transcriptional and metabolite profiles to direct the engineering of lovastatin-producing fungal strains. Nat. Biotechnol. 21 (2003) 150-156. [PMID: 12536215]
2. Awakawa, T., Yokota, K., Funa, N., Doi, F., Mori, N., Watanabe, H. and Horinouchi, S. Physically discrete β-lactamase-type thioesterase catalyzes product release in atrochrysone synthesis by iterative type I polyketide synthase. Chem. Biol. 16 (2009) 613-623. [PMID: 19549600]
3. Lohr, N.A., Eisen, F., Thiele, W., Platz, L., Motter, J., Huttel, W., Gressler, M., Muller, M. and Hoffmeister, D. Unprecedented mushroom polyketide synthases produce the universal anthraquinone precursor. Angew. Chem. Int. Ed. Engl. 61 (2022) e202116142. [PMID: 35218274]
4. Zhao, Q., Zhuang, Z., Liu, T., Yang, Q., He, Q.L., Liu, W. and Lin, G.Q. Unsymmetrically regioselective homodimerization depends on the subcellular colocalization of laccase/fasciclin protein in the biosynthesis of phlegmacins. ACS Chem. Biol. 17 (2022) 791-796. [PMID: 35274920]
5. Lohr, N.A., Urban, M.C., Eisen, F., Platz, L., Huttel, W., Gressler, M., Muller, M. and Hoffmeister, D. The ketosynthase domain controls chain length in mushroom oligocyclic polyketide synthases. Chembiochem 24 (2023) e202200649. [PMID: 36507600]
6. Lohr, N.A., Rakhmanov, M., Wurlitzer, J.M., Lackner, G., Gressler, M. and Hoffmeister, D. Basidiomycete non-reducing polyketide synthases function independently of SAT domains. Fungal Biol Biotechnol 10 (2023) 17. [PMID: 37542286]
7. Throckmorton, K., Lim, F.Y., Kontoyiannis, D.P., Zheng, W. and Keller, N.P. Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus, Environ. Microbiol. 18 (2016) 246-259. [PMID: 26242966]
Accepted name: sulfoacetaldehyde sulfurtransferase
Reaction: a [protein]-S-sulfanyl-L-cysteine + sulfoacetaldehyde + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ = a [protein]-L-cysteine + coenzyme M + 4 oxidized ferredoxin [iron-sulfur] cluster
Glossary: coenzyme M = 2-sulfanylethane-1-sulfonate = 2-mercaptoethanesulfonate
Other name(s): comF (gene name); MJ1681 (locus name)
Systematic name: [protein]-S-sulfanyl-L-cysteine:sulfoacetaldehyde sulfurtransferase
Comments: The enzyme, characterized from the methanogen Methanocaldococcus jannaschii, catalyses the last step in the biosynthesis of coenzyme M. The enzyme carries two [4Fe-4S] clusters. The reaction involves two L-cysteine residues, one of which receives a sulfane sulfur from a donor protein.
References:
1. White, R.H. Identification of an enzyme catalyzing the conversion of sulfoacetaldehyde to 2-mercaptoethanesulfonic acid in methanogens. Biochemistry 58 (2019) 1958-1962. [PMID: 30932481]
Accepted name: 6-deoxy-6-sulfo-D-galactonolactonase
Reaction: 6-deoxy-6-sulfo-D-galactono-1,5-lactone + H2O = 6-deoxy-6-sulfo-D-galactonate
Glossary: 6-deoxy-6-sulfo-D-galactono-1,5-lactone = sulfogalactonolactone
Other name(s): sulfogalactonolactone lactonase; SfcD
Systematic name: 6-deoxy-6-sulfo-D-galactono-1,5-lactone lactonohydrolase
Comments: This enzyme, characterized from the bacterium Paracoccus wurundjeri strain Merri, participates in a sulfofucose degradation pathway. cf. EC 3.1.1.99, 6-deoxy-6-sulfogluconolactonase.
References:
1. Stewart, A.WE., Li, J., Lee, M., Lewis, J.M., Herisse, M., Hofferek, V., McConville, M.J., Pidot, S.J., Scott, N.E. and Williams, S.J. Tandem sulfofucolytic-sulfolactate sulfolyase pathway for catabolism of the rare sulfosugar sulfofucose. mBio 16 (2025) e0184025. [PMID: 40823846]
Accepted name: atrochrysone-2-carbonyl-[acyl-carrier protein] thioesterase
Reaction: (3R)-atrochrysone-2-carbonyl-[acyl-carrier protein] + H2O = (3R)-atrochrysone-2-carboxylate + [acyl-carrier protein]
Glossary: (3R)-atrochrysone-2-carboxylate = (3R)-3,6,8,9-tetrahydroxy-3-methyl-1-oxo-1,2,3,4-tetrahydroanthracene-2-carboxylate
Other name(s): TpcB; ACTE; atrochrysone carboxylate thioesterase
Systematic name: atrochrysone-2-carbonyl-[acyl-carrier protein] hydrolase
Comments: The enzyme was isolated from the mould Aspergillus fumigatus. It is a metallo-β-lactamase type thioesterase.
References:
1. Throckmorton, K., Lim, F.Y., Kontoyiannis, D.P., Zheng, W. and Keller, N.P. Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus, Environ. Microbiol. 18 (2016) 246-259. [PMID: 26242966]
Accepted name: 6-hydroxymusizin-2-carbonyl-[acyl-carrier protein] thioesterase
Reaction: 6-hydroxymusizin-2-carbonyl-[acyl-carrier protein] + H2O = 6-hydroxymusizin + CO2 + [acyl-carrier protein] (overall reaction)
(1a) 6-hydroxymusizin-2-carbonyl-[acyl-carrier protein] + H2O = 6-hydroxymusizin carboxylate + [acyl-carrier protein]
(1b) 6-hydroxymusizin carboxylate = 6-hydroxymusizin + CO2 (spontaneous)
Glossary: 6-hydroxymusizin = (1,6,8-trihydroxynaphthalen-2-yl)ethan-1-one
Systematic name: 6-hydroxymusizin-2-carbonyl-[acyl-carrier protein] hydrolase
Comments: Found in the mushrooms Calonarius odorifer and Calonarius rufo-olivaceus and the mould Chrysosporium merdarium.
References:
1. Thiele, W., Obermaier, S. and Muller, M. A fasciclin protein Is essential for laccase-mediated selective phenol coupling in sporandol biosynthesis. ACS Chem. Biol. 15 (2020) 844-848. [PMID: 32227858]
2. Lohr, N.A., Eisen, F., Thiele, W., Platz, L., Motter, J., Huttel, W., Gressler, M., Muller, M. and Hoffmeister, D. Unprecedented mushroom polyketide synthases produce the universal anthraquinone precursor. Angew. Chem. Int. Ed. Engl. 61 (2022) e202116142. [PMID: 35218274]
3. Lohr, N.A., Urban, M.C., Eisen, F., Platz, L., Huttel, W., Gressler, M., Muller, M. and Hoffmeister, D. The ketosynthase domain controls chain length in mushroom oligocyclic polyketide synthases. Chembiochem 24 (2023) e202200649. [PMID: 36507600]
4. Lohr, N.A., Rakhmanov, M., Wurlitzer, J.M., Lackner, G., Gressler, M. and Hoffmeister, D. Basidiomycete non-reducing polyketide synthases function independently of SAT domains. Fungal Biol Biotechnol 10 (2023) 17. [PMID: 37542286]
Accepted name: ribonuclease P
Reaction: Endonucleolytic cleavage of RNA, removing 5'-extranucleotides from tRNA precursor
Other name(s): RNase P
Comments: The enzyme, which is found in archaea, bacteria and eukaryotes, is essential for tRNA processing. It generates 5'-termini or mature tRNA molecules. The enzyme from most sources has been shown to have an RNA chain and a one or more polypeptide chains, but since the RNA chain can act alone as a catalyst in vitro the enzyme should be considered to be a ribozyme [1,2]. Human mitochondrial RNase P has been shown to be a protein that does not require RNA for activity [3]. Spinach chloroplast RNase P has also been shown to function without an RNA component [4].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Kikovska, E., Svard, S.G. and Kirsebom, L.A. Eukaryotic RNase P RNA mediates cleavage in the absence of protein. Proc. Natl. Acad. Sci. USA 104 (2007) 2062-2067. [PMID: 17284611]
2. Guerrier-Takada, C., Gardiner, K., Marsh, T., Pace, N. and Altman, S. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35 (1983) 849-857. [PMID: 6197186]
3. Holzmann, J., Frank, P., Loffler, E., Bennett, K.L., Gerner, C. and Rossmanith, W. RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme. Cell 135 (2008) 462-474. [PMID: 18984158]
4. Thomas, B.C., Li, X. and Gegenheimer, P. Chloroplast ribonuclease P does not utilize the ribozyme-type pre-tRNA cleavage mechanism. RNA 6 (2000) 545-553. [PMID: 10786845]
Accepted name: galactoligosaccharide 1,2-β-galactosidase
Reaction: Hydrolysis of terminal, non-reducing β-D-galactose residues in (1→2)-β-D-galactooligosaccharides.
Other name(s): β-1,2-galactosidase
Systematic name: galactooligosaccharide exo β-(1,2)-D-galactopyranosidase (non-reducing end)
Comments: The enzyme, characterized from the bacterium Bacteroides xylanisolvens, specifically hydrolyses β-(1,2)-galactopyranosidic bond at the non-reducing end of (1→2)-β-galactooligosaccharides. cf. EC 3.2.1.23, β-galactosidase; EC 3.2.1.108, lactase, and EC 3.2.1.145, galactan 1,3-β-galactosidase.
References:
1. Nakazawa, Y., Kageyama, M., Matsuzawa, T., Liang, Z., Kobayashi, K., Shimizu, H., Maeda, K., Masuhiro, M., Motouchi, S., Kumano, S., Tanaka, N., Kuramochi, K., Nakai, H., Taguchi, H. and Nakajima, M. Structure and function of a β-1,2-galactosidase from Bacteroides xylanisolvens, an intestinal bacterium. Commun Biol 8 (2025) 66. [PMID: 39820076]
Accepted name: guanylurea hydrolase
Reaction: guanylurea + H2O = guanidine + NH3 + CO2 (overall reaction)
(1a) guanylurea + H2O = guanidine + carbamate
(1b) carbamate = NH3 + CO2 (spontaneous)
Other name(s): guuH (gene name)
Systematic name: guanylurea amidohydrolase
Comments: The enzyme, characterized from a strain of the bacterium Pseudomonas mendocina, hydrolyses guanylurea, releasing guanidine and carbamate, which decomposes spontaneously to ammonium and CO2.
References:
1. Tassoulas, L.J., Robinson, A., Martinez-Vaz, B., Aukema, K.G. and Wackett, L.P. Filling in the gaps in metformin biodegradation: a new enzyme and a metabolic pathway for guanylurea. Appl. Environ. Microbiol. 87 (2021) . [PMID: 33741630]
Accepted name: carboxyguanidine deiminase
Reaction: carboxyguanidine + H2O = urea-1-carboxylate + NH3
Glossary: urea-1-carboxylate = allophanate
Other name(s): cgdA (gene name); cgdB (gene name)
Systematic name: carboxyguanidine iminohydrolase
Comments: The enzyme, characterized from the bacterium Pseudomonas syringae, participates in the degradation of guanidine.
References:
1. Schneider, N.O., Tassoulas, L.J., Zeng, D., Laseke, A.J., Reiter, N.J., Wackett, L.P. and Maurice, M.S. Solving the conundrum: widespread proteins annotated for urea metabolism in bacteria are carboxyguanidine deiminases mediating nitrogen assimilation from guanidine. Biochemistry 59 (2020) 3258-3270. [PMID: 32786413]
Accepted name: methylenediurea deaminase
Reaction: methylenediurea + 2 H2O = urea + formaldehyde + 2 NH3 + CO2 (overall reaction)
(1a) methylenediurea + H2O = N-(carboxyaminomethyl)urea + NH3
(1b) N-(carboxyaminomethyl)urea = N-(aminomethyl)urea + CO2 (spontaneous)
(1c) N-(aminomethyl)urea + H2O = N-(hydroxymethyl)urea + NH3
(1d) N-(hydroxymethyl)urea = urea + formaldehyde (spontaneous)
Other name(s): methylenediurease
Systematic name: methylenediurea amidohydrolase
Comments: The enzyme acts on several methyleneurea condensates including trimethylenetetraurea, dimethylenetriurea, and methylenediurea. An initial hydrolysis of the terminal amino group is followed by spontaneous decarboxylation, generating a new terminal amino group. A second hydrolysis generates a terminal hydroxymethyl group that leaves in the form of formaldehyde. The enzyme, characterized from the bacteria Brucella anthropi, Cupriavidus pauculus, and Agrobacterium radiobacter, can also act on allantoate, which is hydrolysed to ureidoglycolate, ammonia and carbon dioxide.
References:
1. Jahns, T., Schepp, R., Kaltwasser, H. Purification and characterisation of an enzyme from a strain of Ochrobactrum anthropi that degrades condensation products of urea and formaldehyde (ureaform). Can. J. Microbiol. 43 (1997) 1111-1117.
2. Jahns, T. and Kaltwasser, H. Mechanism of microbial degradation of slow-release fertilizers. J. Polym. Environ. 8 (2000) 11-16.
3. Jahns, T., Ewen, H. and Kaltwasser, H. Biodegradability of urea-aldehyde condensation products. J. Polym. Environ. 11 (2003) 155-159.
4. Koivunen, M.E., Morisseau, C., Newman, J.W., Horwath, W.R. and Hammock, B.D. Purification and characterization of a methylene urea-hydrolyzing enzyme from Rhizobium radiobacter (Agrobacterium tumefaciens). Soil Biol. Biochem. 35 (2003) 1433-1442.
5. Yang, Z., Shi, Y., Sun, Y., Wang, L. and Guan, F. The study on biodegradation of methylene urea by activated sludge. Polym. Degrad. Stab. 128 (2016) 107-114.
[EC 3.5.3.21 Transferred entry: methylenediurea deaminase. Now EC 3.5.1.141, methylenediurea deaminase. (EC 3.5.3.21 created 1999, deleted 2025)]
[EC 3.6.4.10 Transferred entry: non-chaperonin molecular chaperone ATPase. Now EC 5.6.1.10, non-chaperonin molecular chaperone ATPase (EC 3.6.4.10 created 2000, deleted 2025)]
Accepted name: atrochrysone synthase
Reaction: (3R)-atrochrysone-2-carboxylate = (3R)-atrochrysone + CO2
Glossary: (3R)-atrochrysone-2-carboxylate = (3R)-3,6,8,9-tetrahydroxy-3-methyl-1-oxo-1,2,3,4-tetrahydroanthracene-2-carboxylate
(3R)-atrochrysone = (3R)-3,6,8,9-tetrahydroxy-3-methyl-1-oxo-3,4-dihydroanthracen-1(2H)-one
Other name(s): TpcK; atrochrysone carboxylate decarboxylase
Systematic name: atrochrysone-2-carboxylate carboxyl-lyase
Comments: The enzyme was isolated from the mould Aspergillus fumigatus. Some organisms that form (3R)-atrochrysone lack the enzyme, in which case the uncatalysed reaction appears to be sufficient.
References:
1. Throckmorton, K., Lim, F.Y., Kontoyiannis, D.P., Zheng, W. and Keller, N.P. Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus, Environ. Microbiol. 18 (2016) 246-259. [PMID: 26242966]
Accepted name: 2-dehydro-3,6-dideoxy-6-sulfo-D-galactonate aldolase
Reaction: 2-dehydro-3,6-dideoxy-6-sulfo-D-galactonate = (2S)-3-sulfolactaldehyde + pyruvate
Glossary: 2-dehydro-3,6-dideoxy-6-sulfo-D-galactonate = 3-deoxy-2-ketosulfogalactonate
(2S)-3-sulfolactaldehyde = (2S)-2-hydroxy-3-oxopropane-1-sulfonate
Other name(s): 3-deoxy-2-ketosulfogalactonate aldolase; SfcE
Systematic name: 2-dehydro-3,6-dideoxy-6-sulfo-D-galactonate (2S)-3-sulfolactaldehyde-lyase (pyruvate-forming)
Comments: This enzyme, characterized from the bacterium Paracoccus wurundjeri strain Merri, participates in a sulfofucose degradation pathway. cf. EC 4.1.2.58, 2-dehydro-3,6-dideoxy-6-sulfogluconate aldolase.
References:
1. Stewart, A.WE., Li, J., Lee, M., Lewis, J.M., Herisse, M., Hofferek, V., McConville, M.J., Pidot, S.J., Scott, N.E. and Williams, S.J. Tandem sulfofucolytic-sulfolactate sulfolyase pathway for catabolism of the rare sulfosugar sulfofucose. mBio 16 (2025) e0184025. [PMID: 40823846]
Accepted name: (3S)-3-hydroxy-D-aspartate dehydratase
Reaction: (3S)-3-hydroxy-D-aspartate = 2-iminosuccinate + H2O
Other name(s): bhcB (gene name)
Systematic name: (3S)-3-hydroxy-D-aspartate hydro-lyase
Comments: The enzyme, characterized from the bacterium Paracoccus denitrificans, participates in the the β-hydroxyaspartate cycle of glyoxylate assimilation.
References:
1. Schada von Borzyskowski, L., Severi, F., Kruger, K., Hermann, L., Gilardet, A., Sippel, F., Pommerenke, B., Claus, P., Cortina, N.S., Glatter, T., Zauner, S., Zarzycki, J., Fuchs, B.M., Bremer, E., Maier, U.G., Amann, R.I. and Erb, T.J. Marine Proteobacteria metabolize glycolate via the β-hydroxyaspartate cycle. Nature 575 (2019) 500-504. [PMID: 31723261]
Accepted name: 6-deoxy-6-sulfo-D-galactonate dehydratase
Reaction: 6-deoxy-6-sulfo-D-galactonate = 2-dehydro-3,6-dideoxy-6-sulfo-D-galactonate + H2O
Glossary: 6-deoxy-6-sulfo-D-galactonate = sulfogalactonate
Other name(s): sulfogalactonate dehydratase; SfcF
Systematic name: 6-deoxy-6-sulfo-D-galactonate hydro-lyase (2-dehydro-3,6-dideoxy-6-sulfo-D-galactonate forming)
Comments: This enzyme, characterized from the bacterium Paracoccus wurundjeri strain Merri, participates in a sulfofucose degradation pathway. cf. EC 4.2.1.162, 6-deoxy-6-sulfo-D-gluconate dehydratase.
References:
1. Stewart, A.WE., Li, J., Lee, M., Lewis, J.M., Herisse, M., Hofferek, V., McConville, M.J., Pidot, S.J., Scott, N.E. and Williams, S.J. Tandem sulfofucolytic-sulfolactate sulfolyase pathway for catabolism of the rare sulfosugar sulfofucose. mBio 16 (2025) e0184025. [PMID: 40823846]
Accepted name: 3-cyano-L-homoalanine synthase
Reaction: ATP + L-glutamine = AMP + diphosphate + 2-amino-4-cyanobutanoate (overall reaction)
(1a) ATP + H2O = AMP + diphosphate
(1b) L-glutamine + AMP = (2S)-5-[(5'-adenylyl)oxy]-5-imino-2-aminopentanoate + H2O
(1c) (2S)-5-[(5'-adenylyl)oxy]-5-imino-2-aminopentanoate = 2-amino-4-cyanobutanoate + AMP
Glossary: 2-amino-4-cyanobutanoate = 3-cyano-L-homoalanine = L-γ-cyanohomoalanine
Other name(s): nitB (gene name); artA (gene name)
Systematic name: L-glutamine hydro-lyase (ATP-hydrolysing, 3-cyano-L-homoalanine-forming)
Comments: The enzyme, charaterized from the fungi Penicillium aurantiocandidum and Aspergillus lentulus, participates in the biosynthesis of the the fungal antimicrobial compound auranthine. It is a member of a family of argininosuccinate synthetase (EC 6.3.4.5)-like nitrile synthases that are widespread in fungi and bacteria. Note that while a water molecule is released from L-glutamine, another one is incorporated during the hydrolysis of ATP, and thus the overall reaction does not include water.
References:
1. Kishimoto, S., Tamura, T., Okamoto, T. and Watanabe, K. Enantioselective biosynthesis of (+)- and (–)-auranthines. J. Am. Chem. Soc. 147 (2025) 10612-10617. [PMID: 40099513]
2. Zeng, Y., Zhang, K., Lu, T., Yin, X., Wang, Q., Xiong, L., Guo, H., Li, J., Lu, X., Liu, L., Ma, H. and Gao, Z. Structural and mechanistic basis for nitrile synthetase by an argininosuccinate synthetase-like enzyme. ACS Catalysis (2025) 16254-16267.
Accepted name: levan fructotransferase (DFA-IV-forming)
Reaction: Produces di-β-D-fructofuranose 2,6':2',6-dianhydride (DFA IV) by successively eliminating the diminishing (2→6)-β-D-fructan (levan) chain from the terminal D-fructosyl-D-fructosyl disaccharide
For diagram of reaction, click here
Other name(s): 2,6-β-D-fructan D-fructosyl-D-fructosyltransferase (forming di-β-D-fructofuranose 2,6':2',6-dianhydride); levan fructotransferase; 2,6-β-D-fructan lyase (di-β-D-fructofuranose-2,6':2',6-dianhydride-forming)
Systematic name: (2→6)-β-D-fructan lyase (di-β-D-fructofuranose-2,6':2',6-dianhydride-forming)
Comments: This enzyme, like EC 4.2.2.17 [inulin fructotransferase (DFA-I-forming)] and EC 4.2.2.18 [inulin fructotransferase (DFA-III-forming)], sequentially eliminates disaccharides from the non-reducing terminus of the fructan chain, with the disaccharide leaving as a difructose dianhydride. These enzymes have long been known as fructotransferases, so this is retained in the accepted name. Since the transfer is intramolecular, the reaction is an elimination and, hence, the enzyme is a lyase, belonging in EC 4.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 88593-15-1
References:
1. Song, K.B., Bae, K.S., Lee, Y.B., Lee, K.Y. and Rhee, S.K. Characteristics of levan fructotransferase from Arthrobacter ureafaciens K2032 and difructose anhydride IV formation from levan. Enzyme Microb. Technol. 27 (2000) 212-218. [PMID: 10899545]
2. Jang, K.H., Ryu, E.J., Park, B.S., Song, K.B., Kang, S.A., Kim, C.H., Uhm, T.B., Park, Y.I. and Rhee, S.K. Levan fructotransferase from Arthrobacter oxydans, J 17-21 catalyzes the formation of the di-D-fructose dianhydride IV from levan. J. Agric. Food Chem. 51 (2003) 2632-2636. [PMID: 12696949]
3. Saito, K. and Tomita, F. Difructose anhydrides: Their mass-production and physiological functions. Biosci. Biotechnol. Biochem. 64 (2000) 1321-1327. [PMID: 10945246]
Accepted name: inulin fructotransferase (DFA-I-forming)
Reaction: Produces α-D-fructofuranose β-D-fructofuranose 1,2':2,1'-dianhydride (DFA I) by successively eliminating the diminishing (2→1)-β-D-fructan (inulin) chain from the terminal D-fructosyl-D-fructosyl disaccharide.
For diagram of reaction, click here
Other name(s): inulin fructotransferase (DFA-I-producing); inulin fructotransferase (depolymerizing, difructofuranose-1,2':2',1-dianhydride-forming); inulin D-fructosyl-D-fructosyltransferase (1,2':1',2-dianhydride-forming); inulin D-fructosyl-D-fructosyltransferase (forming α-D-fructofuranose β-D-fructofuranose 1,2':1',2-dianhydride); 2,1-β-D-fructan lyase (α-D-fructofuranose-β-D-fructofuranose-1,2':2,1'-dianhydride-forming)
Systematic name: (2→1)-β-D-fructan lyase (α-D-fructofuranose-β-D-fructofuranose-1,2':2,1'-dianhydride-forming)
Comments: This enzyme, like EC 4.2.2.16 [levan fructotransferase (DFA-IV-forming)] and EC 4.2.2.18 [inulin fructotransferase (DFA-III-forming)], sequentially eliminates disaccharides from the non-reducing terminus of the fructan chain, with the disaccharide leaving as a difructose dianhydride. These enzymes have long been known as fructotransferases, so this is retained in the accepted name. Since the transfer is intramolecular, the reaction is an elimination and, hence, the enzyme is a lyase, belonging in EC 4.
Links to other databases: BRENDA, EXPASY, GENE, KEGG, MetaCyc, PDB, CAS registry number: 125008-19-7
References:
1. Seki, K., Haraguchi, K., Kishimoto, M., Kobayashi, S. and Kainuma, K. Purification and properties of a novel inulin fructotransferase (DFA I-producing) from Arthrobacter globiformis S14-3. Agric. Biol. Chem. 53 (1989) 2089-2094.
Accepted name: inulin fructotransferase (DFA-III-forming)
Reaction: Produces α-D-fructofuranose β-D-fructofuranose 1,2':2,3'-dianhydride (DFA III) by successively eliminating the diminishing (2→1)-β-D-fructan (inulin) chain from the terminal D-fructosyl-D-fructosyl disaccharide.
For diagram of reaction, click here
Other name(s): inulin fructotransferase (DFA-III-producing); inulin fructotransferase (depolymerizing); inulase II; inulinase II; inulin fructotransferase (depolymerizing, difructofuranose-1,2':2,3'-dianhydride-forming); inulin D-fructosyl-D-fructosyltransferase (1,2':2,3'-dianhydride-forming); inulin D-fructosyl-D-fructosyltransferase (forming α-D-fructofuranose β-D-fructofuranose 1,2':2,3'-dianhydride); 2,1-β-D-fructan lyase (α-D-fructofuranose-β-D-fructofuranose-1,2':2,3'-dianhydride-forming)
Systematic name: (2→1)-β-D-fructan lyase (α-D-fructofuranose-β-D-fructofuranose-1,2':2,3'-dianhydride-forming)
Comments: This enzyme, like EC 4.2.2.16 [levan fructotransferase (DFA-IV-forming)] and EC 4.2.2.17 [inulin fructotransferase (DFA-I-forming)], sequentially eliminates disaccharides from the non-reducing terminus of the fructan chain, with the disaccharide leaving as a difructose dianhydride. These enzymes have long been known as fructotransferases, so this is retained in the accepted name. Since the transfer is intramolecular, the reaction is an elimination and, hence, the enzyme is a lyase, belonging in EC 4.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 50936-42-0
References:
1. Uchiyama, T. Action of Arthrobacter ureafaciens inulinase II on several oligofructans and bacterial levans. Biochim. Biophys. Acta 397 (1975) 153-163. [PMID: 1148257]
2. Uchiyama, T., Niwa, S. and Tanaka, K. Purification and properties of Arthrobacter ureafaciens inulase II. Biochim. Biophys. Acta 315 (1973) 412-420.
Accepted name: inulin endo fructotransferase (reducing-end-DFA-III-forming)
Reaction: Cleaves the internal bond of (2→1)-β-D-fructan (inulin) chain and produces α-D-fructofuranose β-D-fructofuranose 1,2':2,3'-dianhydride (DFA III) at the reducing end.
Glossary: DFA = difructose dianhydride
Other name(s): endo-type inulin fructotransferase
Systematic name: endo (2→1)-β-D-fructan lyase (α-D-fructofuranose-β-D-fructofuranose-1,2':2,3'-dianhydride-linked linear (2→1)-β-D-fructofuranoside-forming)
Comments: The enzyme from Bacteroides caccae is a heterodimer composed of large and small subunits, both having a glycoside hydrolase family 91 domain. It cleaves inulin so that one of the products retains the glucosyl residue at the reducing end, while a DFA-III disaccharide is formed at the reducing end of the second product. Unlike this enzyme, inulin fructotransferase (DFA-III-forming) (EC 4.2.2.18) catalyses an exo-type reaction and releases free DFA III.
References:
1. Rakoff-Nahoum, S., Foster, K.R. and Comstock, L.E. The evolution of cooperation within the gut microbiota. Nature 533 (2016) 255-259. [PMID: 27111508]
2. Ishiwata, A., Shite, Y., Kitahara, K., Tanaka, K., Ito, Y. and Fujita, K. Structural analysis of (2→1)-β-D-fructofuranosides linked to a terminal difructose dianhydride III produced by Bacteroides endo-type inulin fructotransferase. Int. J. Biol. Macromol. 310 (2025) 143064. [PMID: 40220837]
Accepted name: pyrogallol-phloroglucinol isomerase
Reaction: 1,2,3-trihydroxybenzene = 1,3,5-trihydroxybenzene (overall reaction)
(1a) 1,2,3-trihydroxybenzene + 3,5-dihydroxycyclohexa-3,5-diene-1,2-dione = 3-hydroxycyclohexa-3,5-diene-1,2-dione + 1,2,3,5-tetrahydroxybenzene
(1b) 3-hydroxycyclohexa-3,5-diene-1,2-dione + [enzyme]-MoVI=O = 3,5-dihydroxycyclohexa-3,5-diene-1,2-dione + [enzyme]-MoIV
(1c) cyclohexa-1,3-diene-1,2,3,5-tetraol + [enzyme]-MoIV = cyclohexa-1,3-diene-1,3,5-triol + [enzyme]-MoVI=O
(1d) cyclohexa-1,3-diene-1,3,5-triol + 1,2,3,5-tetrahydroxybenzene = 1,3,5-trihydroxybenzene + cyclohexa-1,3-diene-1,2,3,5-tetraol
Glossary: 1,2,3-trihydroxybenzene = pyrogallol
1,3,5-trihydroxybenzene = phloroglucinol
Other name(s): pyrogallol hydroxytransferase; 1,2,3,5-tetrahydroxybenzene hydroxyltransferase; 1,2,3,5-tetrahydroxybenzene:pyrogallol transhydroxylase; 1,2,3,5-tetrahydroxybenzene-pyrogallol hydroxyltransferase (transhydroxylase); pyrogallol hydroxyltransferase; 1,2,3,5-tetrahydroxybenzene:1,2,3-trihydroxybenzene hydroxyltransferase
Systematic name: 1,2,3,5-tetrahydroxybenzene:1,2,3-trihydroxybenzene hydroxytransferase
Comments: This molybdoenzyme, characterized from the strictly anaerobic fermenting bacterium Pelobacter acidigallici, transfers the 2-hydroxy group of a molecule of the cofactor 1,2,3,5-tetrahydroxybenzene to pyrogallol (1,2,3-trihydroxybenzene), converting it to a different molecule of 1,2,3,5-tetrahydroxybenzene. Upon loss of the hydroxy group, the original molecule is converted to phloroglucinol (1,3,5-trihydroxybenzene). Unlike most hydroxylating molybdenum enzymes, no water is involved in the reaction.
References:
1. Krumholz, L.R. and Bryant, M.P. Characterization of the pyrogallol-phloroglucinol isomerase of Eubacterium oxidoreducens, J. Bacteriol. 170 (1988) 2472-2479. [PMID: 3372475]
2. Brune, A. and Schink, B. Pyrogallol-to-phloroglucinol conversion and other hydroxyl-transfer reactions catalyzed by cell extracts of Pelobacter acidigallici, J. Bacteriol. 172 (1990) 1070-1076. [PMID: 2298693]
3. Reichenbecher, W., Brune, A. and Schink, B. Transhydroxylase of Pelobacter acidigallici: a molybdoenzyme catalyzing the conversion of pyrogallol to phloroglucinol. Biochim. Biophys Acta 1204 (1994) 217-224. [PMID: 8142462]
4. Reichenbecher, W. and Schink, B. Towards the reaction mechanism of pyrogallol-phloroglucinol transhydroxylase of Pelobacter acidigallici, Biochim. Biophys Acta 1430 (1999) 245-253. [PMID: 10082952]
Accepted name: non-chaperonin molecular chaperone ATPase
Reaction: (1) ATP + H2O + a folded polypeptide = ADP + phosphate + a partially unfolded polypeptide
(2) ATP + H2O + (polypeptide)n = ADP + phosphate + n polypeptide
Other name(s): molecular chaperone Hsc70 ATPase
Systematic name: ATP phosphohydrolase (polypeptide-unfolding)/depolymerizing
Comments: This is a highly diverse group of enzymes that perform many functions that are similar to those of chaperonins. They comprise a number of heat-shock-cognate proteins. They are also active in clathrin uncoating and in the oligomerization of actin. Chaperone binding to exposed hydrophobic segments in polypeptide substrates leads to an ATPase-dependent localized (minor) structural unfolding and a concomitant stabilization against misfolding and aggregation.
References:
1. Sadis, S. and Hightower, L.E. Unfolded proteins stimulate molecular chaperone Hsc70 ATPase by accelerating ADP/ATP exchange. Biochemistry 31 (1992) 9406-9412. [PMID: 1356434]
2. Blond-Elquindi, S., Fourie, A.M., Sambrook, J.F. and Gething, M.J. Peptide-dependent stimulation of the ATPase activity of the molecular chaperone BiP is the result of conversion of oligomers to active monomers. J. Biol. Chem. 268 (1993) 12730-12735. [PMID: 8509407]
3. Wawrzynow, A., Wojtkowiak, D., Marszalek, J., Banecki, B., Jonsen, M., Graves, B., Georgopoulos, C. and Zylicz, M. The ClpX heat-shock protein of Escherichia coli, the ATP-dependent substrate specificity component of the ClpP-ClpX protease, is a novel molecular chaperone. EMBO J. 14 (1995) 1867-1877. [PMID: 7743994]
4. Sriram, M., Osipiuk, J., Freeman, B., Morimoto, R. and Joachimiak, A. Human Hsp70 molecular chaperone binds two calcium ions within the ATPase domain. Structure 5 (1997) 403-414. [PMID: 9083109]
5. Finka, A., Mattoo, R.U. and Goloubinoff, P. Experimental milestones in the discovery of molecular chaperones as polypeptide unfolding enzymes. Annu. Rev. Biochem. 85 (2016) 715-742. [PMID: 27050154]
Accepted name: DNA 5'-3' helicase
Reaction: Couples ATP hydrolysis with the unwinding of duplex DNA at the replication fork by translocating in the 5'-3' direction.
Other name(s): DnaB helicase; replication fork helicase; 5' to 3' DNA helicase; BACH1 helicase; BcMCM; BLM protein; BRCA1-associated C-terminal helicase; CeWRN-1; Dbp9p; DNA helicase A; DNA helicase E; DNA helicase II; DNA helicase III; DNA helicase VI; dnaB (gene name); DnaB helicase E1; helicase HDH IV; Hel E; helicase DnaB; helicase domain of bacteriophage T7 gene 4 protein helicase; PcrA helicase; hHcsA; Hmi1p; hPif1; MCM helicase; MCM protein; MPH1; PcrA; PfDH A; Pfh1p; PIF1; replicative DNA helicase
Systematic name: DNA 5'-3' helicase (ATP-hydrolysing)
Comments: Helicases are motor proteins that can transiently catalyse the unwinding of energetically stable duplex DNA or RNA molecules by using ATP hydrolysis as the source of energy. DNA helicases unwind duplex DNA and are involved in replication, repair, recombination, transcription, pre-rRNA processing, and translation initiation. The best studied DNA 5'-3' helicases are those associated with replication of the chromosome. The activity of the prokaryotic replicative helicase (DnaB) is often stimulated by DNA polymerase III. As the lagging ssDNA is created, it becomes coated with single-stranded DNA binding protein (SSB). Once every 500-2000 nucleotides, primase is stimulated by DnaB helicase to synthesize a primer at the replication fork. This primer is elongated by the lagging strand half of DNA polymerase III holoenzyme.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Lohman, T.M. Helicase-catalyzed DNA unwinding. J. Biol. Chem. 268 (1993) 2269-2272. [PMID: 8381400]
2. Jezewska, M.J. and Bujalowski, W. Global conformational transitions in Escherichia coli primary replicative helicase DnaB protein induced by ATP, ADP, and single-stranded DNA binding. Multiple conformational states of the helicase hexamer. J. Biol. Chem. 271 (1996) 4261-4265. [PMID: 8626772]
3. Ivessa, A.S., Zhou, J.Q., Schulz, V.P., Monson, E.K. and Zakian, V.A. Saccharomyces Rrm3p, a 5' to 3' DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA. Genes Dev. 16 (2002) 1383-1396. [PMID: 12050116]
4. Zhou, J.Q., Qi, H., Schulz, V.P., Mateyak, M.K., Monson, E.K. and Zakian, V.A. Schizosaccharomyces pombe pfh1+ encodes an essential 5' to 3' DNA helicase that is a member of the PIF1 subfamily of DNA helicases. Mol. Biol. Cell 13 (2002) 2180-2191. [PMID: 12058079]
5. Ivanov, K.A. and Ziebuhr, J. Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5'-triphosphatase activities. J. Virol. 78 (2004) 7833-7838. [PMID: 15220459]
6. Toseland, C.P. and Webb, M.R. ATPase mechanism of the 5'-3' DNA helicase, RecD2: evidence for a pre-hydrolysis conformation change. J. Biol. Chem. 288 (2013) 25183-25193. [PMID: 23839989]
Accepted name: 3-(methylthio)propionate—CoA ligase
Reaction: ATP + 3-(methylsulfanyl)propanoate + CoA = AMP + diphosphate + 3-(methylsulfanyl)propanoyl-CoA
For diagram of 3-(dimethylsulfonio)propanoate metabolism, click here
Other name(s): DmdB; MMPA-CoA ligase; 3-(methylthio)propanoate—CoA ligase; methylmercaptopropionate-coenzyme A ligase; 3-methylmercaptopropionate-CoA ligase; 3-(methylthio)propanoate:CoA ligase (AMP-forming)
Systematic name: 3-(methylsulfanyl)propanoate:CoA ligase (AMP-forming)
Comments: The enzyme is part of a dimethylsulfoniopropanoate demethylation pathway in the marine bacteria Ruegeria pomeroyi and Pelagibacter ubique. It also occurs in some nonmarine bacteria capable of metabolizing dimethylsulfoniopropionate (e.g. Burkholderia thailandensis, Pseudomonas aeruginosa, and Silicibacter lacuscaerulensis). It requires Mg2+ [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Reisch, C.R., Stoudemayer, M.J., Varaljay, V.A., Amster, I.J., Moran, M.A. and Whitman, W.B. Novel pathway for assimilation of dimethylsulphoniopropionate widespread in marine bacteria. Nature 473 (2011) 208-211. [PMID: 21562561]
2. Bullock, H.A., Reisch, C.R., Burns, A.S., Moran, M.A. and Whitman, W.B. Regulatory and functional diversity of methylmercaptopropionate coenzyme A ligases from the dimethylsulfoniopropionate demethylation pathway in Ruegeria pomeroyi DSS-3 and other proteobacteria. J. Bacteriol. 196 (2014) 1275-1285. [PMID: 24443527]
Accepted name: urea carboxylase
Reaction: ATP + urea + hydrogencarbonate = ADP + phosphate + urea-1-carboxylate
Glossary: urea-1-carboxylate = allophanate
Other name(s): urease (ATP-hydrolysing); urea carboxylase (hydrolysing); ATP—urea amidolyase; urea amidolyase; UALase; UCA
Systematic name: urea:carbon-dioxide ligase (ADP-forming)
Comments: A biotinyl-protein. The yeast enzyme (but not that from green algae) is bifunctional (resulting from gene fusion) and also catalyses the reaction of EC 3.5.1.54 allophanate hydrolase, thus bringing about the hydrolysis of urea to CO2 and NH3. cf. EC 6.3.4.26, guanidine carboxylase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9058-98-4
References:
1. Roon, R.J. and Levenberg, B. ATP-Urea amidolyase (ADP) (Candida utilis). Methods Enzymol. 17A (1970) 317-324.
2. Roon, R.J. and Levenberg, B. Urea amidolyase. I. Properties of the enzyme from Candida utilis, J. Biol. Chem. 247 (1972) 4107-4113. [PMID: 4556303]
3. Sumrada, R.A. and Cooper, T.G. Urea carboxylase and allophanate hydrolase are components of a multifunctional protein in yeast. J. Biol. Chem. 257 (1982) 9119-9127. [PMID: 6124544]
Accepted name: 7-cyano-7-deazaguanine synthase
Reaction: 2 ATP + NH3 + 7-carboxy-7-carbaguanine = 2 AMP + 2 diphosphate + 7-cyano-7-carbaguanine (overall reaction)
(1a) ATP + 7-carboxy-7-carbaguanine = diphosphate + 7-carboxyadenylyl-7-carbaguanine
(1b) NH3 + 7-carboxyadenylyl-7-carbaguanine = AMP + 7-amido-7-carbaguanine
(1c) ATP + 7-amido-7-carbaguanine = diphosphate + 7-iminomethyladenylyl-7-carbaguanine
(1d) 7-iminomethyladenylyl-7-carbaguanine = AMP + 7-cyano-7-carbaguanine
For diagram of queuine biosynthesis, click here
Glossary: preQ0 = 7-cyano-7-carbaguanine = 7-cyano-7-deazaguanine
7-carboxy-7-carbaguanine = 7-carboxy-7-deazaguanine
7-carboxyadenylyl-7-carbaguanine = 2-amino-4-oxo-3H,4H,7H-pyrrolo[2,3-d]pyrimidine-5-carboxyadenylate
7-iminomethyladenylyl-7-carbaguanine = 2-amino-4-oxo-3H,4H,7H-pyrrolo[2,3-d]pyrimidine-5-carboximidyl-adenylate
Other name(s): preQ0 synthase; 7-cyano-7-carbaguanine synthase; queC (gene name); toyM (gene name); 7-carboxy-7-carbaguanine:ammonia ligase (ADP-forming)
Systematic name: 7-carboxy-7-carbaguanine:ammonia ligase (AMP-forming)
Comments: Binds Zn2+. The enzyme is found in bacteria and archaea.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. McCarty, R.M., Somogyi, A., Lin, G., Jacobsen, N.E. and Bandarian, V. The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of preQ0 from guanosine 5'-triphosphate in four steps. Biochemistry 48 (2009) 3847-3852. [PMID: 19354300]
2. Cicmil, N. and Huang, R.H. Crystal structure of QueC from Bacillus subtilis: an enzyme involved in preQ1 biosynthesis. Proteins 72 (2008) 1084-1088. [PMID: 18491386]
3. Nelp, M.T. and Bandarian, V. A single enzyme transforms a carboxylic acid into a nitrile through an amide intermediate. Angew. Chem. Int. Ed. Engl. 54 (2015) 10627-10629. [PMID: 26228534]
Accepted name: guanidine carboxylase
Reaction: ATP + guanidine + hydrogencarbonate = ADP + phosphate + carboxyguanidine
Systematic name: guanidine:carbon-dioxide ligase (ADP-forming)
Comments: A biotinyl-protein. This bacterial enzyme is similar to EC 6.3.4.6, urea carboxylase, yet unlike the fungal enzyme it displays a strong substrate preference for guanidine over urea. In addition, unlike the fungal enzyme, which is bifunctional, the bacterial enzyme is monofunctional. The enzyme participates in a pathway for guanidine degradation to ammonia and CO2.
References:
1. Kanamori, T., Kanou, N., Atomi, H. and Imanaka, T. Enzymatic characterization of a prokaryotic urea carboxylase. J. Bacteriol. 186 (2004) 2532-2539. [PMID: 15090492]
2. Nelson, J.W., Atilho, R.M., Sherlock, M.E., Stockbridge, R.B. and Breaker, R.R. Metabolism of free guanidine in bacteria Is regulated by a widespread riboswitch class. Mol. Cell 65 (2017) 220-230. [PMID: 27989440]
3. Schneider, N.O., Tassoulas, L.J., Zeng, D., Laseke, A.J., Reiter, N.J., Wackett, L.P. and Maurice, M.S. Solving the conundrum: widespread proteins annotated for urea metabolism in bacteria are carboxyguanidine deiminases mediating nitrogen assimilation from guanidine. Biochemistry 59 (2020) 3258-3270. [PMID: 32786413]