An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: UDP-N-acetyl-α-D-quinovosamine dehydrogenase
Reaction: UDP-N-acetyl-α-D-quinovosamine + NAD(P)+ = UDP-2-acetamido-2,6-dideoxy-α-D-xylohex-4-ulose + NAD(P)H + H+
Glossary: UDP-N-acetyl-α-D-quinovosamine = UDP-N-acetyl-6-deoxy-α-D-glucosamine
Other name(s): wbpV (gene name); wreQ (gene name)
Systematic name: UDP-N-acetyl-α-D-quinovosamine:NAD(P)+ 4-dehydrogenase
Comments: The enzyme participates in the biosynthesis of N-acetyl-α-D-quinovosamine, a 6-deoxy sugar that is present in the O antigens of many Gram-negative bacteria, including Pseudomonas aeruginosa serotypes O6 and O10, Rhizobium etli, and Brucella abortus.
References:
1. Belanger, M., Burrows, L.L. and Lam, J.S. Functional analysis of genes responsible for the synthesis of the B-band O antigen of Pseudomonas aeruginosa serotype O6 lipopolysaccharide. Microbiology (Reading) 145 (1999) 3505-3521. [PMID: 10627048]
2. Forsberg, L.S., Noel, K.D., Box, J. and Carlson, R.W. Genetic locus and structural characterization of the biochemical defect in the O-antigenic polysaccharide of the symbiotically deficient Rhizobium etli mutant, CE166. Replacement of N-acetylquinovosamine with its hexosyl-4-ulose precursor. J. Biol. Chem. 278 (2003) 51347-51359. [PMID: 14551189]
3. Li, T., Simonds, L., Kovrigin, E.L. and Noel, K.D. In vitro biosynthesis and chemical identification of UDP-N-acetyl-D-quinovosamine (UDP-D-QuiNAc). J. Biol. Chem. 289 (2014) 18110-18120. [PMID: 24817117]
Accepted name: fructose 5-dehydrogenase
Reaction: D-fructose + an ubiquinone = 5-dehydro-D-fructose + an ubiquinol
Other name(s): fructose 5-dehydrogenase (acceptor); D-fructose dehydrogenase; D-fructose:(acceptor) 5-oxidoreductase
Systematic name: D-fructose:ubiquinone 5-oxidoreductase
Comments: The enzyme, characterized from the bacterium Gluconobacter japonicus, is a heterotrimer composed of an FAD-containing large subunit, a small subunit, and a heme c-containing subunit, which is responsible for anchoring the complex to the cytoplasmic membrane and for transferring the electrons to ubiquinone.
References:
1. Yamada, Y., Aida, K. and Uemura, T. Enzymatic studies on the oxidation of sugar and sugar alcohol. I. Purification and properties of particle-bound fructose dehydrogenase. J. Biochem. (Tokyo) 61 (1967) 636-646. [PMID: 6059959]
2. Ameyama, M. and Adachi, O. D-Fructose dehydrogenase from Gluconobacter industrius, membrane-bound. Methods Enzymol. 89 (1982) 154-159.
3. Nakashima, K., Takei, H., Adachi, O., Shinagawa, E. and Ameyama, M. Determination of seminal fructose using D-fructose dehydrogenase. Clin. Chim. Acta 151 (1985) 307-310. [PMID: 4053391]
4. Kawai, S., Goda-Tsutsumi, M., Yakushi, T., Kano, K. and Matsushita, K. Heterologous overexpression and characterization of a flavoprotein-cytochrome c complex fructose dehydrogenase of Gluconobacter japonicus NBRC3260. Appl. Environ. Microbiol. 79 (2013) 1654-1660. [PMID: 23275508]
[EC 1.1.99.11 Transferred entry: fructose 5-dehydrogenase, now classified as EC 1.1.5.14, fructose 5-dehydrogenase. (EC 1.1.99.11 created 1972, deleted 2021.)]
Accepted name: glutarate-semialdehyde dehydrogenase
Reaction: 5-oxopentanoate + NADP+ + H2O = glutarate + NADPH + H+
Glossary: 5-oxopentanoate = glutarate semialdehyde
Other name(s): glutarate semialdehyde dehydrogenase; davD (gene name)
Systematic name: glutarate-semialdehyde:NADP+ oxidoreductase
Comments: The enzyme, characterized from multiple Pseudomonas strains, participates in L-lysine degradation. Unlike earlier claims, it prefers NADP+ to NAD+.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9028-99-3
References:
1. Ichihara, A. and Ichihara, E.A. Metabolism of L-lysine by bacterial enzymes. V. Glutaric semialdehyde dehydrogenase. J. Biochem. (Tokyo) 49 (1961) 154-157. [PMID: 13717359]
2. Chang, Y. F. and Adams, E. Glutaric semialdehyde dehydrogenase (Pseudomonas putida). Methods Enzymol. 17B (1971) 166-171.
3. Fothergill, J.C. and Guest, J.R. Catabolism of L-lysine by Pseudomonas aeruginosa. J. Gen. Microbiol. 99 (1977) 139-155. [PMID: 405455]
4. Chang, Y.F. and Adams, E. Glutarate semialdehyde dehydrogenase of Pseudomonas. Purification, properties, and relation to L-lysine catabolism. J. Biol. Chem. 252 (1977) 7979-7986. [PMID: 914857]
5. Yamanishi, Y., Mihara, H., Osaki, M., Muramatsu, H., Esaki, N., Sato, T., Hizukuri, Y., Goto, S. and Kanehisa, M. Prediction of missing enzyme genes in a bacterial metabolic network. Reconstruction of the lysine-degradation pathway of Pseudomonas aeruginosa. FEBS J. 274 (2007) 2262-2273. [PMID: 17388807]
Accepted name: glyceraldehyde-3-phosphate dehydrogenase (arsenate-transferring)
Reaction: D-glyceraldehyde 3-phosphate + arsenate + NAD+ = 1-arsono-3-phospho-D-glycerate + NADH + H+
Glossary: 1-arsono-3-phosphoglycerate = [(2R)-2-hydroxy-3-phosphopropanoyl]oxyarsonate
Systematic name: D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (arsenate-transferring)
Comments: The enzyme, discovered in bacteria, is very similar to EC 1.2.1.12, glyceraldehyde-3-phosphate dehydrogenase (phosphorylating). However, the gene encoding it is located in arsenic resistance islands in the chromosome, next to a gene (arsJ) that encodes a transporter that removes the product, 1-arseno-3-phosphoglycerate, from the cell. Together the two proteins form an arsenic detoxification system.
References:
1. Chen, J., Yoshinaga, M., Garbinski, L.D. and Rosen, B.P. Synergistic interaction of glyceraldehydes-3-phosphate dehydrogenase and ArsJ, a novel organoarsenical efflux permease, confers arsenate resistance. Mol. Microbiol. 100 (2016) 945-953. [PMID: 26991003]
2. Wu, S., Wang, L., Gan, R., Tong, T., Bian, H., Li, Z., Du, S., Deng, Z. and Chen, S. Signature arsenic detoxification pathways in Halomonas sp. strain GFAJ-1. mBio 9 (2018) . [PMID: 29717010]
Accepted name: fatty acid α-dioxygenase
Reaction: a fatty acid + O2 = a (2R)-2-hydroperoxyfatty acid
Other name(s): DOX1 (gene name)
Systematic name: fatty acid:oxygen 2-oxidoreductase [(2R)-2-hydroperoxyfatty acid-forming]
Comments: Contains heme. This plant enzyme catalyses the (2R)-hydroperoxidation of fatty acids. It differs from lipoxygenases and cyclooxygenases in that the oxygen addition does not target an unsaturated region in the fatty acid. In vitro the product undergoes spontaneous decarboxylation, resulting in formation of a chain-shortened aldehyde. In vivo the product may be reduced to a (2R)-2-hydroxyfatty acid. The enzyme, which is involved in responses to different abiotic and biotic stresses, has a wide substrate range that includes both saturated and unsaturated fatty acids.
References:
1. Akakabe, Y., Matsui, K., and Kajiwara, T. Enantioselective α-hydroperoxylation of long-chain fatty acids with crude enzyme of marine green alga Ulva pertusa. Tetrahedron Lett. 40 (1999) 1137-1140.
2. Hamberg, M., Sanz, A. and Castresana, C. α-oxidation of fatty acids in higher plants. Identification of a pathogen-inducible oxygenase (piox) as an α-dioxygenase and biosynthesis of 2-hydroperoxylinolenic acid. J. Biol. Chem. 274 (1999) 24503-24513. [PMID: 10455113]
3. Saffert, A., Hartmann-Schreier, J., Schon, A. and Schreier, P. A dual function α-dioxygenase-peroxidase and NAD(+) oxidoreductase active enzyme from germinating pea rationalizing α-oxidation of fatty acids in plants. Plant Physiol. 123 (2000) 1545-1552. [PMID: 10938370]
4. Koeduka, T., Matsui, K., Akakabe, Y. and Kajiwara, T. Catalytic properties of rice α-oxygenase. A comparison with mammalian prostaglandin H synthases. J. Biol. Chem. 277 (2002) 22648-22655. [PMID: 11909851]
5. Liu, W., Rogge, C.E., Bambai, B., Palmer, G., Tsai, A.L. and Kulmacz, R.J. Characterization of the heme environment in Arabidopsis thaliana fatty acid α-dioxygenase-1. J. Biol. Chem. 279 (2004) 29805-29815. [PMID: 15100225]
6. Meisner, A.K., Saffert, A., Schreier, P. and Schon, A. Fatty acid α-dioxygenase from Pisum sativum: temporal and spatial regulation during germination and plant development. J. Plant Physiol. 166 (2009) 333-343. [PMID: 18760499]
Accepted name: alkyl sulfatase
Reaction: a primary alkyl sulfate ester + 2-oxoglutarate + O2 = an aldehyde + succinate + CO2 + sulfate
Other name(s): atsK (gene name); α-ketoglutarate-dependent sulfate ester dioxygenase; 2-oxoglutarate-dependent sulfate ester dioxygenase; type II alkyl sulfatase
Systematic name: primary alkyl sulfate ester, 2-oxoglutarate:oxygen oxidoreductase (sulfate-hydrolyzing)
Comments: Sulfatase enzymes are classified as type I, in which the key catalytic residue is 3-oxo-L-alanine, type II, which are non-heme iron-dependent dioxygenases, or type III, whose catalytic domain adopts a metallo-β-lactamase fold and binds two zinc ions as cofactors. The type II sulfatases oxidize the C-H bond of the carbon next to the sulfate ester, using 2-oxoglutarate and oxygen as substrates. The resulting hemiacetal sulfate ester collapses, liberating inorganic sulfate and an alkyl aldehyde along with carbon dioxide and succinate. The enzymes often desulfate a broad spectrum of linear and branched-chain sulfate esters. The enzyme from Pseudomonas putida acts on a range of medium-chain alkyl sulfate esters, with chain lengths ranging from C4 to C12. cf. sulfatase EC 3.1.6.1, arylsulfatase (type I), EC 3.1.6.21, linear primary-alkylsulfatase, and EC 3.1.6.22, branched primary-alkylsulfatase.
References:
1. Kahnert, A. and Kertesz, M.A. Characterization of a sulfur-regulated oxygenative alkylsulfatase from Pseudomonas putida S-313. J. Biol. Chem. 275 (2000) 31661-31667. [PMID: 10913158]
2. Muller, I., Kahnert, A., Pape, T., Sheldrick, G.M., Meyer-Klaucke, W., Dierks, T., Kertesz, M. and Uson, I. Crystal structure of the alkylsulfatase AtsK: insights into the catalytic mechanism of the Fe(II) α-ketoglutarate-dependent dioxygenase superfamily. Biochemistry 43 (2004) 3075-3088. [PMID: 15023059]
3. Sogi, K.M., Gartner, Z.J., Breidenbach, M.A., Appel, M.J., Schelle, M.W. and Bertozzi, C.R. Mycobacterium tuberculosis Rv3406 is a type II alkyl sulfatase capable of sulfate scavenging. PLoS One 8 (2013) e65080. [PMID: 23762287]
Accepted name: cyanocobalamin reductase
Reaction: 2 cob(II)alamin-[cyanocobalamin reductase] + 2 hydrogen cyanide + NADP+ = 2 cyanocob(III)alamin + 2 [cyanocobalamin reductase] + NADPH + H+
Other name(s): MMACHC (gene name); CblC; cyanocobalamin reductase (NADPH, cyanide-eliminating); cyanocobalamin reductase (NADPH, CN-eliminating); NADPH:cyanocob(III)alamin oxidoreductase (cyanide-eliminating); cob(I)alamin, cyanide:NADP+ oxidoreductase; cyanocobalamin reductase (cyanide-eliminating)
Systematic name: cob(II)alamin, hydrogen cyanide:NADP+ oxidoreductase
Comments: The mammalian enzyme, which is cytosolic, can bind internalized cyanocobalamin and process it to cob(II)alamin by removing the upper axial ligand. The product remains bound to the protein, which, together with its interacting partner MMADHC, transfers it directly to downstream enzymes involved in adenosylcobalamin and methylcobalamin biosynthesis. In addition to its decyanase function, the mammalian enzyme also catalyses an entirely different chemical reaction with alkylcobalamins, using the thiolate of glutathione for nucleophilic displacement, generating cob(I)alamin and the corresponding glutathione thioether (cf. EC 2.5.1.151, alkylcobalamin dealkylase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 131145-00-1
References:
1. Watanabe, F., Oki, Y., Nakano, Y. and Kitaoka, S. Occurrence and characterization of cyanocobalamin reductase (NADPH; CN-eliminating) involved in decyanation of cyanocobalamin in Euglena gracilis. J. Nutr. Sci. Vitaminol. 34 (1988) 1-10. [PMID: 3134526]
2. Kim, J., Gherasim, C. and Banerjee, R. Decyanation of vitamin B12 by a trafficking chaperone. Proc. Natl. Acad. Sci. USA 105 (2008) 14551-14554. [PMID: 18779575]
3. Koutmos, M., Gherasim, C., Smith, J.L. and Banerjee, R. Structural basis of multifunctionality in a vitamin B12-processing enzyme. J. Biol. Chem. 286 (2011) 29780-29787. [PMID: 21697092]
4. Mah, W., Deme, J.C., Watkins, D., Fung, S., Janer, A., Shoubridge, E.A., Rosenblatt, D.S. and Coulton, J.W. Subcellular location of MMACHC and MMADHC, two human proteins central to intracellular vitamin B12 metabolism. Mol Genet Metab 108 (2013) 112-118. [PMID: 23270877]
EC 1.16.99 With unknown physiological acceptors
Accepted name: [Co(II) methylated amine-specific corrinoid protein] reductase
Reaction: (1) ATP + a [Co(II) methylamine-specific corrinoid protein] + reduced acceptor + H2O = ADP + phosphate + a [Co(I) methylamine-specific corrinoid protein] + acceptor
(2) ATP + a [Co(II) dimethylamine-specific corrinoid protein] + reduced acceptor + H2O = ADP + phosphate + a [Co(I) dimethylamine-specific corrinoid protein] + acceptor
(3) ATP + a [Co(II) trimethylamine-specific corrinoid protein] + reduced acceptor + H2O = ADP + phosphate + a [Co(I) trimethylamine-specific corrinoid protein] + acceptor
Glossary: ramA (gene name)
Systematic name: acceptor:[cobalt(II) methylated amines-specific corrinoid protein] oxidoreductase (ATP-hydrolysing)
Comments: Methyltrophic corrinoid proteins must have the cobalt atom in the active cobalt(I) state to become methylated. Because the cobalt(I)/cobalt(II) transformation has a very low redox potential the corrinoid cofactor is subject to adventitious oxidation to the cobalt(II) state, which renders the proteins inactive. This enzyme, characterized from the methanogenic archaeon Methanosarcina barkeri, reduces cobalt(II) back to cobalt(I), restoring activity. The enzyme acts on the corrinoid proteins involved in methanogenesis from methylamine, dimethylamine, and trimethylamine, namely MtmC, MtbC, and MttC, respectively. While in vitro the enzyme can use Ti(III)-citrate as the electron donor, the in vivo donor is not known. The enzyme from Methanosarcina barkeri contains a C-terminal [4Fe-4S] ferredoxin-like domain.
References:
1. Ferguson, T., Soares, J.A., Lienard, T., Gottschalk, G. and Krzycki, J.A. RamA, a protein required for reductive activation of corrinoid-dependent methylamine methyltransferase reactions in methanogenic archaea. J. Biol. Chem. 284 (2009) 2285-2295. [PMID: 19043046]
2. Durichen, H., Diekert, G. and Studenik, S. Redox potential changes during ATP-dependent corrinoid reduction determined by redox titrations with europium(II)-DTPA. Protein Sci. 28 (2019) 1902-1908. [PMID: 31359509]
Accepted name: methyltransferase cap1
Reaction: S-adenosyl-L-methionine + a 5'-(N7-methyl 5'-triphosphoguanosine)-(ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N7-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleotide)-[mRNA]
Other name(s): FTSJD2 (gene name); messenger ribonucleate nucleoside 2'-methyltransferase; messenger RNA (nucleoside-2'-)-methyltransferase; MTR1; cap1-MTase; mRNA (nucleoside-2'-O)-methyltransferase (ambiguous); S-adenosyl-L-methionine:mRNA (nucleoside-2'-O)-methyltransferase
Systematic name: S-adenosyl-L-methionine:5-(N7-methyl 5-triphosphoguanosine)-(ribonucleotide)-[mRNA] 2-O-methyltransferase
Comments: This enzyme catalyses the methylation of the ribose on the first transcribed nucleotide of mRNA or snRNA molecules. This methylation event is known as cap1, and occurs in all mRNAs and snRNAs of higher eukaryotes, including insects, vertebrates and their viruses. The human enzyme can also methylate mRNA molecules that lack methylation on the capping 5'-triphosphoguanosine [6].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 61970-02-3
References:
1. Barbosa, E. and Moss, B. mRNA(nucleoside-2'-)-methyltransferase from vaccinia virus. Purification and physical properties. J. Biol. Chem. 253 (1978) 7692-7697. [PMID: 701281]
2. Barbosa, E. and Moss, B. mRNA(nucleoside-2'-)-methyltransferase from vaccinia virus. Characteristics and substrate specificity. J. Biol. Chem. 253 (1978) 7698-7702. [PMID: 701282]
3. Boone, R.F., Ensinger, M.J. and Moss, B. Synthesis of mRNA guanylyltransferase and mRNA methyltransferases in cells infected with vaccinia virus. J. Virol. 21 (1977) 475-483. [PMID: 833934]
4. Ensinger, M.J., Martin, S.A., Paoletti, E. and Moss, B. Modification of the 5'-terminus of mRNA by soluble guanylyl and methyl transferases from vaccinia virus. Proc. Natl. Acad. Sci. USA 72 (1975) 2525-2529. [PMID: 1058472]
5. Groner, Y., Gilbao, E. and Aviv, H. Methylation and capping of RNA polymerase II primary transcripts by HeLa nuclear homogenates. Biochemistry 17 (1978) 977-982. [PMID: 629955]
6. Werner, M., Purta, E., Kaminska, K.H., Cymerman, I.A., Campbell, D.A., Mittra, B., Zamudio, J.R., Sturm, N.R., Jaworski, J. and Bujnicki, J.M. 2'-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family. Nucleic Acids Res. 39 (2011) 4756-4768. [PMID: 21310715]
Accepted name: tRNA 5-(aminomethyl)-2-thiouridylate-methyltransferase
Reaction: S-adenosyl-L-methionine + tRNA containing 5-(aminomethyl)-2-thiouridine = S-adenosyl-L-homocysteine + tRNA containing 5-[(methylamino)methyl]-2-thiouridylate
Other name(s): transfer ribonucleate 5-methylaminomethyl-2-thiouridylate 5-methyltransferase; tRNA 5-methylaminomethyl-2-thiouridylate 5'-methyltransferase; S-adenosyl-L-methionine:tRNA (5-methylaminomethyl-2-thio-uridylate)-methyltransferase; tRNA (5-methylaminomethyl-2-thiouridylate)-methyltransferase
Systematic name: S-adenosyl-L-methionine:tRNA 5-(aminomethyl)-2-thiouridylate N-methyltransferase
Comments: This enzyme specifically adds the terminal methyl group of 5-[(methylamino)methyl]-2-thiouridylate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 39391-17-8
References:
1. Taya, Y. and Nishimura, S. Biosynthesis of 5-methylaminomethyl-2-thiouridylate. I. Isolation of a new tRNA-methylase specific for 5-methylaminomethyl-2-thiouridylate. Biochem. Biophys. Res. Commun. 51 (1973) 1062-1068. [PMID: 4703553]
2. Taya, Y. and Nishimura, S. In: Salvatore, F., Borek, E., Zappia, V., Williams-Ashman, H.G. and Schlenk, F. (Ed.), The Biochemistry of Adenosylmethionine, Columbia University Press, New York, 1977, p. 251.
3. Bujnicki, J.M., Oudjama, Y., Roovers, M., Owczarek, S., Caillet, J. and Droogmans, L. Identification of a bifunctional enzyme MnmC involved in the biosynthesis of a hypermodified uridine in the wobble position of tRNA. RNA 10 (2004) 1236-1242. [PMID: 15247431]
4. Kim, J. and Almo, S.C. Structural basis for hypermodification of the wobble uridine in tRNA by bifunctional enzyme MnmC. BMC Struct Biol 13 (2013) 5. [PMID: 23617613]
Accepted name: methyltransferase cap2
Reaction: S-adenosyl-L-methionine + a 5'-(N7-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleotide)-(ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N7-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleotide)-(2'-O-methyl-ribonucleotide)-[mRNA]
Other name(s): CMTR2 (gene name); MTR2; cap2-MTase; mRNA (nucleoside-2'-O)-methyltransferase (ambiguous)
Systematic name: S-adenosyl-L-methionine:5'-(N7-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleotide)-ribonucleotide-[mRNA] 2'-O-methyltransferase
Comments: The enzyme, found in higher eukaryotes including insects and vertebrates, and their viruses, methylates the ribose of the ribonucleotide at the second transcribed position of mRNAs and snRNAs. This methylation event is known as cap2. The human enzyme can also methylate mRNA molecules where the upstream purine ribonucleotide is not methylated (see EC 2.1.1.57, methyltransferase cap1), but with lower efficiency [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Arhin, G.K., Ullu, E. and Tschudi, C. 2'-O-methylation of position 2 of the trypanosome spliced leader cap 4 is mediated by a 48 kDa protein related to vaccinia virus VP39. Mol. Biochem. Parasitol. 147 (2006) 137-139. [PMID: 16516986]
2. Werner, M., Purta, E., Kaminska, K.H., Cymerman, I.A., Campbell, D.A., Mittra, B., Zamudio, J.R., Sturm, N.R., Jaworski, J. and Bujnicki, J.M. 2'-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family. Nucleic Acids Res. 39 (2011) 4756-4768. [PMID: 21310715]
Accepted name: glycine betaine—corrinoid protein Co-methyltransferase
Reaction: glycine betaine + a [Co(I) glycine betaine-specific corrinoid protein] = N,N-dimethylglycine + a [methyl-Co(III) glycine betaine-specific corrinoid protein]
Other name(s): mtgB (gene name); glycine betaine methyltransferase
Systematic name: glycine betaine:[Co(I) glycine betaine-specific corrinoid protein] Co-methyltransferase
Comments: The enzyme, which catalyses the transfer of a methyl group from glycine betaine to a glycine betaine-specific corrinoid protein (MtgC), is involved in methanogenesis from glycine betaine in some methanogenic archaea, and in glycine betaine degradation in some bacteria. Unlike similar enzymes involved in methanogenesis from methylated C1 compounds, this enzyme does not contain the unusual amino acid L-pyrrolysine.
References:
1. Ticak, T., Kountz, D.J., Girosky, K.E., Krzycki, J.A. and Ferguson, D.J., Jr. A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase. Proc. Natl. Acad. Sci. USA 111 (2014) E4668-E4676. [PMID: 25313086]
2. Creighbaum, A.J., Ticak, T., Shinde, S., Wang, X. and Ferguson, D.J., Jr. Examination of the glycine betaine-dependent methylotrophic methanogenesis pathway: insights into anaerobic quaternary amine methylotrophy. Front. Microbiol. 10 (2019) 2572. [PMID: 31787957]
Accepted name: [methyl-Co(III) glycine betaine-specific corrinoid protein]—coenzyme M methyltransferase
Reaction: a [methyl-Co(III) glycine betaine-specific corrinoid protein] + CoM = methyl-CoM + a [Co(I) glycine betaine-specific corrinoid protein]
Other name(s): mtaA (gene name)
Systematic name: methylated glycine betaine-specific corrinoid protein:CoM methyltransferase
Comments: The enzyme, which is involved in methanogenesis from glycine betaine, catalyses the transfer of a methyl group bound to the cobalt cofactor of glycine betaine-specific corrinoid protein to coenzyme M, forming the substrate for EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase, which catalyses the final step in methanogenesis. The enzyme from the methanogenic archaeon Methanolobus vulcani B1d can also catalyse the activity of EC 2.1.1.246, [methyl-Co(III) methanol-specific corrinoid protein]—coenzyme M methyltransferase.
References:
1. Creighbaum, A.J., Ticak, T., Shinde, S., Wang, X. and Ferguson, D.J., Jr. Examination of the glycine betaine-dependent methylotrophic methanogenesis pathway: insights into anaerobic quaternary amine methylotrophy. Front. Microbiol. 10 (2019) 2572. [PMID: 31787957]
Accepted name: [methyl-Co(III) glycine betaine-specific corrinoid protein]—tetrahydrofolate methyltransferase
Reaction: a [methyl-Co(III) glycine betaine-specific corrinoid protein] + tetrahydrofolate = a [Co(I) glycine betaine-specific corrinoid protein] + 5-methyltetrahydrofolate
Other name(s): mtgA (gene name); DSY3157 (locus name)
Systematic name: [methyl-Co(III) glycine betaine-specific corrinoid protein]:tetrahydrofolate N-methyltransferase
Comments: This enzyme, characterized from the anaerobic bacterium Desulfitobacterium hafniense Y51, catalyses a similar reaction to that of EC 2.1.1.258, 5-methyltetrahydrofolate—corrinoid/iron-sulfur protein Co-methyltransferase, but in the opposite direction, transferring a methyl group from a methylated corrinoid protein to tetrahydrofolate. The corrinoid protein is specifically methylated by EC 2.1.1.376, glycine betaine—corrinoid protein Co-methyltransferase.
References:
1. Ticak, T., Kountz, D.J., Girosky, K.E., Krzycki, J.A. and Ferguson, D.J., Jr. A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase. Proc. Natl. Acad. Sci. USA 111 (2014) E4668-E4676. [PMID: 25313086]
Accepted name: [methyl coenzyme M reductase]-L-arginine C-5-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + a [methyl coenzyme-M reductase]-L-arginine + reduced acceptor = S-adenosyl-L-homocysteine + L-methionine + 5'-deoxyadenosine + a [methyl coenzyme-M reductase]-(5S)-C-methyl-L-arginine + acceptor
Other name(s): methanogenesis marker protein 10; Mmp10
Systematic name: S-adenosyl-L-methionine:[methyl coenzyme M reductase]-L-arginine C-5-(S)-methyltransferase
Comments: The enzyme, present in methanogenic archaea, catalyses a modification of an L-arginine residue at the active site of EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase (better known as methyl-coenzyme M reductase), which catalyses the last and methane-releasing step of methanogenesis. The enzyme is a radical AdoMet (radical SAM) enzyme and contains a [4Fe-4S] cluster and a Coα-[α-(5-hydroxybenzimidazolyl)]-cobamide cofactor. The methyl group, which is derived from S-adenosyl-L-methionine, is transferred to the cob(I)amide cofactor, forming methylcob(III)amide as an intermediate carrier, before being transferred to the arginine residue.
References:
1. Deobald, D., Adrian, L., Schone, C., Rother, M. and Layer, G. Identification of a unique radical SAM methyltransferase required for the sp3-C-methylation of an arginine residue of methyl-coenzyme M reductase. Sci. Rep. 8 (2018) 7404. [PMID: 29743535]
2. Radle, M.I., Miller, D.V., Laremore, T.N. and Booker, S.J. Methanogenesis marker protein 10 (Mmp10) from Methanosarcina acetivorans is a radical S-adenosylmethionine methylase that unexpectedly requires cobalamin. J. Biol. Chem. 294 (2019) 11712-11725. [PMID: 31113866]
3. Lyu, Z., Shao, N., Chou, C.W., Shi, H., Patel, R., Duin, E.C. and Whitman, W.B. Posttranslational methylation of arginine in methyl coenzyme M reductase has a profound impact on both methanogenesis and growth of Methanococcus maripaludis. J. Bacteriol. 202 (2020) . [PMID: 31740491]
Accepted name: GDP-perosamine N-formyltransferase
Reaction: 10-formyltetrahydrofolate + GDP-α-D-perosamine = tetrahydrofolate + GDP-N-formyl-α-D-perosamine
Glossary: GDP-α-D-perosamine = GDP-4-amino-4,6-dideoxy-α-D-mannose
Other name(s): wbkC (gene name)
Systematic name: 10-formyltetrahydrofolate:GDP-α-D-perosamine N-formyltransferase
Comments: The enzyme, characterized from the bacterium Brucella melitensis, synthesizes a building block of the O antigen produced by Brucella species.
References:
1. Godfroid, F., Cloeckaert, A., Taminiau, B., Danese, I., Tibor, A., de Bolle, X., Mertens, P. and Letesson, J.J. Genetic organisation of the lipopolysaccharide O-antigen biosynthesis region of Brucella melitensis 16M (wbk). Res. Microbiol. 151 (2000) 655-668. [PMID: 11081580]
2. Riegert, A.S., Chantigian, D.P., Thoden, J.B., Tipton, P.A. and Holden, H.M. Biochemical Characterization of WbkC, an N-Formyltransferase from Brucella melitensis. Biochemistry 56 (2017) 3657-3668. [PMID: 28636341]
Accepted name: UDP-3-O-(3-hydroxyacyl)glucosamine N-acyltransferase
Reaction: a (3R)-3-hydroxyacyl-[acyl-carrier protein] + a UDP-3-O-[(3R)-3-hydroxyacyl]-α-D-glucosamine = a UDP-2-N,3-O-bis[(3R)-3-hydroxyacyl]-α-D-glucosamine + a holo-[acyl-carrier protein]
For diagram of reaction click here
Other name(s): lpxD (gene name); UDP-3-O-acyl-glucosamine N-acyltransferase; UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase; acyltransferase LpxD; acyl-ACP:UDP-3-O-(3-hydroxyacyl)-GlcN N-acyltransferase; firA (gene name); (3R)-3-hydroxymyristoyl-[acyl-carrier protein]:UDP-3-O-[(3R)-3-hydroxymyristoyl]-α-D-glucosamine N-acetyltransferase; UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase; (3R)-3-hydroxytetradecanoyl-[acyl-carrier protein]:UDP-3-O-[(3R)-3-hydroxytetradecanoyl]-α-D-glucosamine N-acetyltransferase
Systematic name: (3R)-3-hydroxyacyl-[acyl-carrier protein]:UDP-3-O-[(3R)-3-hydroxyacyl]-α-D-glucosamine N-acyltransferase
Comments: The enzyme catalyses a step of lipid A biosynthesis. LpxD from Escherichia coli prefers (3R)-3-hydroxytetradecanoyl-[acyl-carrier protein] [3], but it does not have an absolute specificity for 14-carbon hydroxy fatty acids, as it can transfer other fatty acids, including odd-chain fatty acids, if they are available to the organism [5].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Kelly, T.M., Stachula, S.A., Raetz, C.R. and Anderson, M.S. The firA gene of Escherichia coli encodes UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase. The third step of endotoxin biosynthesis. J. Biol. Chem. 268 (1993) 19866-19874. [PMID: 8366125]
2. Buetow, L., Smith, T.K., Dawson, A., Fyffe, S. and Hunter, W.N. Structure and reactivity of LpxD, the N-acyltransferase of lipid A biosynthesis. Proc. Natl. Acad. Sci. USA 104 (2007) 4321-4326. [PMID: 17360522]
3. Bartling, C.M. and Raetz, C.R. Steady-state kinetics and mechanism of LpxD, the N-acyltransferase of lipid A biosynthesis. Biochemistry 47 (2008) 5290-5302. [PMID: 18422345]
4. Bainbridge, B.W., Karimi-Naser, L., Reife, R., Blethen, F., Ernst, R.K. and Darveau, R.P. Acyl chain specificity of the acyltransferases LpxA and LpxD and substrate availability contribute to lipid A fatty acid heterogeneity in Porphyromonas gingivalis. J. Bacteriol. 190 (2008) 4549-4558. [PMID: 18456814]
5. Bartling, C.M. and Raetz, C.R. Crystal structure and acyl chain selectivity of Escherichia coli LpxD, the N-acyltransferase of lipid A biosynthesis. Biochemistry 48 (2009) 8672-8683. [PMID: 19655786]
6. Badger, J., Chie-Leon, B., Logan, C., Sridhar, V., Sankaran, B., Zwart, P.H. and Nienaber, V. Structure determination of LpxD from the lipopolysaccharide-synthesis pathway of Acinetobacter baumannii. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 69 (2013) 6-9. [PMID: 23295477]
7. Kroeck, K.G., Sacco, M.D., Smith, E.W., Zhang, X., Shoun, D., Akhtar, A., Darch, S.E., Cohen, F., Andrews, L.D., Knox, J.E. and Chen, Y. Discovery of dual-activity small-molecule ligands of Pseudomonas aeruginosa LpxA and LpxD using SPR and X-ray crystallography. Sci. Rep. 9 (2019) 15450. [PMID: 31664082]
Accepted name: poly[(R)-3-hydroxyalkanoate] polymerase
Reaction: (3R)-3-hydroxyacyl-CoA + poly[(R)-3-hydroxyalkanoate]n = CoA + poly[(R)-3-hydroxyalkanoate]n+1
Other name(s): PHA synthase; phaC (gene name); PhaE
Systematic name: poly(R)-3-hydroxyalkanoate (3R)-3-hydroxyacyltransferase
Comments: This is the key enzyme in the biosynthesis of polyhydroxyalkanoates (PHA), linear polyesters produced by bacteria as a means of carbon and energy storage [6]. The enzyme catalyses the stereoselective, covalent linkage of (3R)-3-hydroxyacyl-CoA thioesters in a transesterification reaction with concomitant release of coenzyme A. The growing polymer is attached to a conserved active site L-cysteine residue. Three types of PHA synthases have been proposed based on their substrate specificity and enzyme structure. Type I and type III synthases preferentially polymerize short chain hydroxyalkanoate monomers containing 3-5 carbon atoms [1,2]. The difference between these two types is that type I synthases are composed of only a single subunit (PhaC), whereas type III synthases are composed of two different subunits, PhaC and PhaE [3,5]. Type II synthases are also composed of a single subunit (PhaC), but preferentially polymerize monomers containing more than 5 carbon atoms [4].
References:
1. Anderson, A.J., Haywood, G.W. and Dawes, E.A. Biosynthesis and composition of bacterial poly(hydroxyalkanoates). Int. J. Biol. Macromol. 12 (1990) 102-105. [PMID: 2078525]
2. Liebergesell, M., Sonomoto, K., Madkour, M., Mayer, F. and Steinbuchel, A. Purification and characterization of the poly(hydroxyalkanoic acid) synthase from Chromatium vinosum and localization of the enzyme at the surface of poly(hydroxyalkanoic acid) granules. Eur. J. Biochem. 226 (1994) 71-80. [PMID: 7957260]
3. Muh, U., Sinskey, A.J., Kirby, D.P., Lane, W.S. and Stubbe, J. PHA synthase from Chromatium vinosum: cysteine 149 is involved in covalent catalysis. Biochemistry 38 (1999) 826-837. [PMID: 9888824]
4. Ren, Q., De Roo, G., Kessler, B. and Witholt, B. Recovery of active medium-chain-length-poly-3-hydroxyalkanoate polymerase from inactive inclusion bodies using ion-exchange resin. Biochem. J. 349 (2000) 599-604. [PMID: 10880359]
5. Jia, Y., Yuan, W., Wodzinska, J., Park, C., Sinskey, A.J. and Stubbe, J. Mechanistic studies on class I polyhydroxybutyrate (PHB) synthase from Ralstonia eutropha: class I and III synthases share a similar catalytic mechanism. Biochemistry 40 (2001) 1011-1019. [PMID: 11170423]
6. Zou, H., Shi, M., Zhang, T., Li, L., Li, L. and Xian, M. Natural and engineered polyhydroxyalkanoate (PHA) synthase: key enzyme in biopolyester production. Appl. Microbiol. Biotechnol. 101 (2017) 7417-7426. [PMID: 28884324]
Accepted name: lipid-A-disaccharide synthase
Reaction: a UDP-2-N,3-O-bis[(3R)-3-hydroxyacyl]-α-D-glucosamine + a lipid X = UDP + a lipid A disaccharide
For diagram of lreaction click here
Glossary: a lipid X = 2-N-[(3R)-3-hydroxyacyl]-3-O-[(3R)-3-hydroxyacyl]-α-D-glucosamine 1-phosphate =
2-N,3-O-bis[(3R)-3-hydroxyacyl]-α-D-glucosamine
a lipid A disaccharide = a 2-deoxy-2-{[(3R)-3-hydroxyacyl]amino}-3-O-[(3R)-3-hydroxyacyl]-β-D-glucopyranosyl-(1→6)-2-deoxy-3-O-[(3R)-3-hydroxyacyl]-2-{[(3R)-3-hydroxyacyl]amino}-1-O-phospho-α-D-glucopyranose
Other name(s): lpxB (gene name); UDP-2,3-bis(3-hydroxytetradecanoyl)glucosamine:2,3-bis-(3-hydroxytetradecanoyl)-β-D-glucosaminyl-1-phosphate 2,3-bis(3-hydroxytetradecanoyl)-glucosaminyltransferase (incorrect)
Systematic name: UDP-2-N,3-O-bis[(3R)-3-hydroxyacyl]-α-D-glucosamine:2-N,3-O-bis[(3R)-3-hydroxyacyl]-α-D-glucosamine 1-phosphate 2-N,3-O-bis[(3R)-3-hydroxyacyl]-α-D-glucosaminyltransferase
Comments: Involved with EC 2.3.1.129 (acyl-[acyl-carrier-protein]—UDP-N-acetylglucosamine O-acyltransferase) and EC 2.7.1.130 (tetraacyldisaccharide 4'-kinase) in the biosynthesis of the phosphorylated glycolipid, lipid A, in the outer membrane of Gram-negative bacteria.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 105843-81-0
References:
1. Ray, B.L., Painter, G. and Raetz, C.R.H. The biosynthesis of gram-negative endotoxin. Formation of lipid A disaccharides from monosaccharide precursors in extracts of Escherichia coli. J. Biol. Chem. 259 (1984) 4852-4859. [PMID: 6370995]
2. Crowell, D.N., Reznikoff, W.S. and Raetz, C.R.H. Nucleotide sequence of the Escherichia coli gene for lipid A disaccharide synthase. J. Bacteriol. 169 (1987) 5727-5734. [PMID: 2824445]
3. Metzger, L.E., 4th and Raetz, C.R. Purification and characterization of the lipid A disaccharide synthase (LpxB) from Escherichia coli, a peripheral membrane protein. Biochemistry 48 (2009) 11559-11571. [PMID: 19883124]
4. Bohl, T.E., Shi, K., Lee, J.K. and Aihara, H. Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli. Nat. Commun. 9 (2018) 377. [PMID: 29371662]
Accepted name: NDP-glycosyltransferase
Reaction: an NDP-glycose + an acceptor = a glycosylated acceptor + NDP
Other name(s): yjiC (gene name)
Systematic name: NDP-glycose:acceptor glycosyltransferase
Comments: The enzyme, characterized from the bacterium Bacillus licheniformis DSM-13, is an extremely promiscuous glycosyltransferase. It can accept ADP-, GDP-, CDP-, TDP-, or UDP-activated glycose molecules as donors, and can glycosylate a large number of substrates, catalysing O-, N-, or S-glycosylation. While D-glucose is the primarily reported sugar being transferred, the enzyme has been shown to transfer D-galactose, 2-deoxy-D-glucose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, L-fucose, L-rhamnose, D-glucuronate, and D-viosamine.
References:
1. Pandey, R.P., Parajuli, P., Koirala, N., Park, J.W. and Sohng, J.K. Probing 3-hydroxyflavone for in vitro glycorandomization of flavonols by YjiC. Appl. Environ. Microbiol. 79 (2013) 6833-6838. [PMID: 23974133]
2. Pandey, R.P., Gurung, R.B., Parajuli, P., Koirala, N., Tuoi le, T. and Sohng, J.K. Assessing acceptor substrate promiscuity of YjiC-mediated glycosylation toward flavonoids. Carbohydr. Res. 393 (2014) 26-31. [PMID: 24893262]
3. Pandey, R.P., Parajuli, P., Shin, J.Y., Lee, J., Lee, S., Hong, Y.S., Park, Y.I., Kim, J.S. and Sohng, J.K. Enzymatic biosynthesis of novel resveratrol glucoside and glycoside derivatives. Appl. Environ. Microbiol. 80 (2014) 7235-7243. [PMID: 25239890]
4. Parajuli, P., Pandey, R.P., Koirala, N., Yoon, Y.J., Kim, B.G. and Sohng, J.K. Enzymatic synthesis of epothilone A glycosides. AMB Express 4 (2014) 31. [PMID: 24949266]
5. Pandey, R.P., Parajuli, P., Gurung, R.B. and Sohng, J.K. Donor specificity of YjiC glycosyltransferase determines the conjugation of cytosolic NDP-sugar in in vivo glycosylation reactions. Enzyme Microb. Technol. 91 (2016) 26-33. [PMID: 27444326]
6. Bashyal, P., Thapa, S.B., Kim, T.S., Pandey, R.P. and Sohng, J.K. Exploring the nucleophilic N- and S-glycosylation capacity of Bacillus licheniformis YjiC enzyme. J. Microbiol. Biotechnol. 30 (2020) 1092-1096. [PMID: 32238768]
Accepted name: pyrimidine-nucleoside phosphorylase
Reaction: (1) uridine + phosphate = uracil + α-D-ribose 1-phosphate
(2) cytidine + phosphate = cytosine + α-D-ribose 1-phosphate
(3) 2'-deoxyuridine + phosphate = uracil + 2-deoxy-α-D-ribose 1-phosphate
(4) thymidine + phosphate = thymine + 2-deoxy-α-D-ribose 1-phosphate
Other name(s): Py-NPase; pdp (gene name)
Systematic name: pyrimidine-nucleoside:phosphate (2'-deoxy)-α-D-ribosyltransferase
Comments: Unlike EC 2.4.2.3, uridine phosphorylase, and EC 2.4.2.4, thymidine phosphorylase, this enzyme can accept both the ribonucleosides uridine and cytidine and the 2'-deoxyribonucleosides 2'-deoxyuridine and thymidine [3,6]. The reaction is reversible, and the enzyme does not distinguish between α-D-ribose 1-phosphate and 2-deoxy-α-D-ribose 1-phosphate in the synthetic direction.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9055-35-0
References:
1. Friedkin, M. and Kalckar, H. Nucleoside phosphorylases. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Ed.), The Enzymes, 2nd edn, vol. 5, Academic Press, New York, 1961, pp. 237-255.
2. Saunders, P.P., Wilson, B.A. and Saunders, G.F. Purification and comparative properties of a pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus. J. Biol. Chem. 244 (1969) 3691-3697. [PMID: 4978445]
3. Hamamoto, T., Noguchi, T. and Midorikawa, Y. Purification and characterization of purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus TH 6-2. Biosci. Biotechnol. Biochem. 60 (1996) 1179-1180. [PMID: 8782414]
4. Okuyama, K., Hamamoto, T., Noguchi, T. and Midorikawa, Y. Molecular cloning and expression of the pyrimidine nucleoside phosphorylase gene from Bacillus stearothermophilus TH 6-2. Biosci. Biotechnol. Biochem. 60 (1996) 1655-1659. [PMID: 8987664]
5. Pugmire, M.J. and Ealick, S.E. The crystal structure of pyrimidine nucleoside phosphorylase in a closed conformation. Structure 6 (1998) 1467-1479. [PMID: 9817849]
6. Wei, X.K., Ding, Q.B., Zhang, L., Guo, Y.L., Ou, L. and Wang, C.L. Induction of nucleoside phosphorylase in Enterobacter aerogenes and enzymatic synthesis of adenine arabinoside. J Zhejiang Univ Sci B 9 (2008) 520-526. [PMID: 18600781]
Accepted name: putrescine—2-oxoglutarate transaminase
Reaction: putrescine + 2-oxoglutarate = 4-aminobutanal + L-glutamate
For diagram of reaction click here
Glossary: putrescine = butane-1,4-diamine
1-pyrroline = 3,4-dihydro-2H-pyrrole
Other name(s): putrescine-α-ketoglutarate transaminase; YgjG; putrescine:α-ketoglutarate aminotransferase; PAT (ambiguous); putrescine transaminase (ambiguous); putrescine aminotransferase (ambiguous); butane-1,4-diamine:2-oxoglutarate aminotransferase
Systematic name: putrescine:2-oxoglutarate aminotransferase
Comments: A pyridoxal 5'-phosphate protein [3]. The product, 4-aminobutanal, spontaneously cyclizes to form 1-pyrroline, which may be the actual substrate for EC 1.2.1.19, aminobutyraldehyde dehydrogenase. Cadaverine and spermidine can also act as substrates [3]. Forms part of the arginine-catabolism pathway [2]. cf. EC 2.6.1.113, putrescine—pyruvate transaminase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 98982-73-1
References:
1. Prieto-Santos, M.I., Martin-Checa, J., Balaña-Fouce, R. and Garrido-Pertierra, A. A pathway for putrescine catabolism in Escherichia coli. Biochim. Biophys. Acta 880 (1986) 242-244. [PMID: 3510672]
2. Samsonova, N.N., Smirnov, S.V., Novikova, A.E. and Ptitsyn, L.R. Identification of Escherichia coli K12 YdcW protein as a γ-aminobutyraldehyde dehydrogenase. FEBS Lett. 579 (2005) 4107-4112. [PMID: 16023116]
3. Samsonova, N.N., Smirnov, S.V., Altman, I.B. and Ptitsyn, L.R. Molecular cloning and characterization of Escherichia coli K12 ygjG gene. BMC Microbiol. 3 (2003) 2. [PMID: 12617754]
Accepted name: 6-phosphofructokinase
Reaction: ATP + β-D-fructofuranose 6-phosphate = ADP + β-D-fructofuranose 1,6-bisphosphate
For diagram of reaction click here
Other name(s): phosphohexokinase; phosphofructokinase I; phosphofructokinase (phosphorylating); 6-phosphofructose 1-kinase; ATP-dependent phosphofructokinase; D-fructose-6-phosphate 1-phosphotransferase; fructose 6-phosphate kinase; fructose 6-phosphokinase; nucleotide triphosphate-dependent phosphofructokinase; phospho-1,6-fructokinase; PFK
Systematic name: ATP:β-D-fructose-6-phosphate 1-phosphotransferase
Comments: The enzyme from rabbit muscle displays absolute stereoselectivity for the β-anomer of D-fructofuranose 6-phosphate [9-11]. D-Tagatose 6-phosphate and sedoheptulose 7-phosphate can act as acceptors. UTP, CTP and ITP can act as donors. Not identical with EC 2.7.1.105 6-phosphofructo-2-kinase.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9001-80-3
References:
1. Racker, E. Spectrophotometric measurement of hexokinase and phosphohexokinase activity. J. Biol. Chem. 167 (1947) 843-854. [PMID: 20287918]
2. Axelrod, B., Saltman, P., Bandurski, R.S. and Baker, R.S. Hexokinase in higher plants. J. Biol. Chem. 197 (1952) 89-96. [PMID: 12981037]
3. Ling, K.H., Pastkau, V., Marcus, F. and Lardy, H.A. Phosphofructokinase. I. Skeletal muscle. Methods Enzymol. 9 (1966) 425-429.
4. Mansour, T.E. Phosphofructokinase. II. Heart muscle. Methods Enzymol. 9 (1966) 430-436.
5. Parmeggiano, A., Luft, J.H., Love, D.S. and Krebs, E.G. Crystallization and properties of rabbit skeletal muscle phosphofructokinase. J. Biol. Chem. 241 (1966) 4625-4637. [PMID: 4224472]
6. Sols, A. and Salas, M.L. Phosphofructokinase. III. Yeast. Methods Enzymol. 9 (1966) 436-442.
7. Odeide, R., Guilloton, M., Dupuis, B., Ravon, D. and Rosenberg, A.J. Study of an enzyme allosteric to 2 substrates: phosphofructokinase of rat muscle. I. Preparation and crystallization of the enzyme. Bull. Soc. Chim. Biol. 50 (1968) 2023-2033. [PMID: 4237772]
8. Uyeda, K. and Kurooka, S. Crystallization and properties of phosphofructokinase from Clostridium pasteurianum. J. Biol. Chem. 245 (1970) 3315-3324. [PMID: 4248230]
9. Fishbein, R., Benkovic, P.A., Schray, K.J., Siewers, I.J., Steffens, J.J. and Benkovic, S.J. Anomeric specificity of phosphofructokinase from rabbit muscle. J. Biol. Chem. 249 (1974) 6047-6051. [PMID: 4278654]
10. Wurster, B. and Hess, B. Anomeric specificity of fructose-6-phosphate kinase (EC 2.7.1.11) from rabbit muscle. FEBS Lett. 38 (1974) 257-260. [PMID: 4277364]
11. Koerner, T.A., Jr., Younathan, E.S., Ashour, A.L. and Voll, R.J. The fructose 6-phosphate site of phosphofructokinase. I. Tautomeric and anomeric specificity. J. Biol. Chem. 249 (1974) 5749-5754. [PMID: 4278316]
Accepted name: apulose kinase
Reaction: ATP + apulose = ADP + apulose 4-phosphate
Glossary: apulose = 1,3,4-trihydroxy-3-(hydroxymethyl)butan-2-one
Other name(s): aplK (gene name)
Systematic name: ATP:apulose 4-phosphotransferase
Comments: The enzyme, characterized from several bacterial species, is involved in a catabolic pathway for D-apiose.
References:
1. Carter, M.S., Zhang, X., Huang, H., Bouvier, J.T., Francisco, B.S., Vetting, M.W., Al-Obaidi, N., Bonanno, J.B., Ghosh, A., Zallot, R.G., Andersen, H.M., Almo, S.C. and Gerlt, J.A. Functional assignment of multiple catabolic pathways for D-apiose. Nat. Chem. Biol. 14 (2018) 696-705. [PMID: 29867142]
Accepted name: fatty acid kinase
Reaction: ATP + a fatty acid = ADP + a fatty acyl phosphate (overall reaction)
(1a) ATP + a fatty acid-[fatty acid-binding protein] = ADP + a fatty acyl phosphate-[fatty acid-binding protein]
(1b) a fatty acyl phosphate-[fatty acid-binding protein] + a fatty acid = a fatty acyl phosphate + a fatty acid-[fatty acid-binding protein]
Other name(s): fakAB (gene names)
Systematic name: ATP:fatty acid 1-phosphotransferase
Comments: The enzyme is a dimeric complex consisting of an ATP-binding protein (FakA) and a fatty acid-binding protein (FakB). The first step in the reaction is the binding of FakB (with a bound fatty acid) to FakA. The fatty acid bound to FakB is then phosphorylated by FakA, and the fatty acyl phosphate-bound FakB is released from the complex. In the presence of an exchangeable fatty acid pool in the cell membrane, the fatty acy phosphate bound to FakB exchanges with a fatty acid to regenerate the substrate for FakA. The system is widespread in Gram-positive bacteria, with most strains possessing a single FakA protein along with multiple FakB subunits that differ in their specificity towards fatty acid substrates.
References:
1. Parsons, J.B., Frank, M.W., Jackson, P., Subramanian, C. and Rock, C.O. Incorporation of extracellular fatty acids by a fatty acid kinase-dependent pathway in Staphylococcus aureus. Mol. Microbiol. 92 (2014) 234-245. [PMID: 24673884]
2. Parsons, J.B., Broussard, T.C., Bose, J.L., Rosch, J.W., Jackson, P., Subramanian, C. and Rock, C.O. Identification of a two-component fatty acid kinase responsible for host fatty acid incorporation by Staphylococcus aureus. Proc. Natl. Acad. Sci. USA 111 (2014) 10532-10537. [PMID: 25002480]
3. Broussard, T.C., Miller, D.J., Jackson, P., Nourse, A., White, S.W. and Rock, C.O. Biochemical roles for conserved residues in the bacterial fatty acid-binding protein family. J. Biol. Chem. 291 (2016) 6292-6303. [PMID: 26774272]
[EC 2.7.7.58 Transferred entry: (2,3-dihydroxybenzoyl)adenylate synthase. Now included in EC 6.2.1.71, 2,3-dihydroxybenzoate[aryl-carrier protein] ligase (EC 2.7.7.58 created 1992, deleted 2021)]
Accepted name: ω-hydroxy-β-dihydromenaquinone-9 sulfotransferase
Reaction: 3'-phosphoadenylyl sulfate + ω-hydroxy-β-dihydromenaquinone-9 = adenosine 3',5'-bisphosphate + ω-sulfo-β-dihydromenaquinone-9
Glossary: β-dihydromenaquinone-9 = MK-9(II-H2) = 2-methyl-3-[(2E,10E,14E,18E,22E,26E,30E,33E)-3,7,11,15,19,23,27,31,35-nonamethylhexatriaconta-2,10,14,18,22,26,30,33-octaen-1-yl]naphthalene-1,4-dione
Other name(s): stf3 (gene name)
Systematic name: 3'-phosphoadenylyl-sulfate:ω-hydroxy-β-dihydromenaquinone-9 sulfotransferase
Comments: The enzyme catalyses the last step in the production of ω-sulfo-β-dihydromenaquinone-9 by members of the Mycobacterium tuberculosis complex.
References:
1. Mougous, J.D., Senaratne, R.H., Petzold, C.J., Jain, M., Lee, D.H., Schelle, M.W., Leavell, M.D., Cox, J.S., Leary, J.A., Riley, L.W. and Bertozzi, C.R. A sulfated metabolite produced by stf3 negatively regulates the virulence of Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 103 (2006) 4258-4263. [PMID: 16537518]
2. Holsclaw, C.M., Sogi, K.M., Gilmore, S.A., Schelle, M.W., Leavell, M.D., Bertozzi, C.R. and Leary, J.A. Structural characterization of a novel sulfated menaquinone produced by stf3 from Mycobacterium tuberculosis. ACS Chem. Biol. 3 (2008) 619-624. [PMID: 18928249]
Accepted name: phospholipid sn-1 acylhydrolase
Reaction: (1) a 1-phosphatidyl-1D-myo-inositol + H2O = a 2-acyl-sn-glycero-3-phospho-1D-myo-inositol + a fatty acid
(2) a 1,2-diacyl-sn-glycerol 3-phosphate + H2O = a 2-acyl-sn-glycerol 3-phosphate + a fatty acid
Glossary: a 1,2-diacyl-sn-glycerol 3-phosphate = a phosphatidate
Other name(s): phospholipase DDHD1; phosphatidic acid-preferring phospholipase A1; PA-PLA1; DDHD1 (gene name)
Systematic name: phospholipid sn-1 acylhydrolase
Comments: The human enzyme shows broad specificity, and has a preference for phosphatidate over other phospholipids. Unlike EC 3.1.1.32, phospholipase A1, it is also active against phosphatidylinositol. It is not active towards acyl groups linked at the sn-2 position.
References:
1. Yamashita, A., Kumazawa, T., Koga, H., Suzuki, N., Oka, S. and Sugiura, T. Generation of lysophosphatidylinositol by DDHD domain containing 1 (DDHD1): Possible involvement of phospholipase D/phosphatidic acid in the activation of DDHD1. Biochim. Biophys. Acta 1801 (2010) 711-720. [PMID: 20359546]
2. Baba, T., Kashiwagi, Y., Arimitsu, N., Kogure, T., Edo, A., Maruyama, T., Nakao, K., Nakanishi, H., Kinoshita, M., Frohman, M.A., Yamamoto, A. and Tani, K. Phosphatidic acid (PA)-preferring phospholipase A1 regulates mitochondrial dynamics. J. Biol. Chem. 289 (2014) 11497-11511. [PMID: 24599962]
Accepted name: arylsulfatase (type I)
Reaction: an aryl sulfate + H2O = a phenol + sulfate
Other name(s): sulfatase; nitrocatechol sulfatase; phenolsulfatase; phenylsulfatase; p-nitrophenyl sulfatase; arylsulfohydrolase; 4-methylumbelliferyl sulfatase; estrogen sulfatase; type I sulfatase; arylsulfatase
Systematic name: aryl-sulfate sulfohydrolase
Comments: Sulfatase enzymes are classified as type I, in which the key catalytic residue is 3-oxo-L-alanine, type II, which are non-heme iron-dependent dioxygenases, or type III, whose catalytic domain adopts a metallo-β-lactamase fold and binds two zinc ions as cofactors. Arylsulfatases are type I enzymes, found in both prokaryotes and eukaryotes, with rather similar specificities. The key catalytic residue 3-oxo-L-alanine initiates the reaction through a nucleophilic attack on the sulfur atom in the substrate. This residue is generated by posttranslational modification of a conserved cysteine or serine residue by EC 1.8.3.7, formylglycine-generating enzyme, EC 1.1.98.7, serine-type anaerobic sulfatase-maturating enzyme, or EC 1.8.98.7, cysteine-type anaerobic sulfatase-maturating enzyme.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9016-17-5
References:
1. Dodgson, K.S., Spencer, B. and Williams, K. Studies on sulphatases. 13. The hydrolysis of substituted phenyl sulphates by the arylsulphatase of Alcaligenes metacaligenes. Biochem. J. 64 (1956) 216-221. [PMID: 13363831]
2. Webb, E.C. and Morrow, P.F.W. The activation of an arysulphatase from ox liver by chloride and other anions. Biochem. J. 73 (1959) 7-15. [PMID: 13843260]
3. Roy, A.B. The synthesis and hydrolysis of sulfate esters. Adv. Enzymol. Relat. Subj. Biochem. 22 (1960) 205-235. [PMID: 13744184]
4. Roy, A.B. Sulphatases, lysosomes and disease. Aust. J. Exp. Biol. Med. Sci. 54 (1976) 111-135. [PMID: 13772]
5. Schmidt, B., Selmer, T., Ingendoh, A. and von Figura, K. A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency. Cell 82 (1995) 271-278. [PMID: 7628016]
6. Dierks, T., Miech, C., Hummerjohann, J., Schmidt, B., Kertesz, M.A. and von Figura, K. Posttranslational formation of formylglycine in prokaryotic sulfatases by modification of either cysteine or serine. J. Biol. Chem. 273 (1998) 25560-25564. [PMID: 9748219]
Accepted name: (R)-specific secondary-alkylsulfatase (type III)
Reaction: an (R)-secondary-alkyl sulfate + H2O = an (S)-secondary-alcohol + sulfate
Other name(s): S3 secondary alkylsulphohydrolase; Pisa1; secondary alkylsulphohydrolase; (R)-specific sec-alkylsulfatase; sec-alkylsulfatase; (R)-specific secondary-alkylsulfatase
Systematic name: (R)-secondary-alkyl sulfate sulfohydrolase [(S)-secondary-alcohol forming]
Comments: Sulfatase enzymes are classified as type I, in which the key catalytic residue is 3-oxo-L-alanine, type II, which are non-heme iron-dependent dioxygenases, or type III, whose catalytic domain adopts a metallo-β-lactamase fold and binds two zinc ions as cofactors. This enzyme belongs to the type III sulfatase family. The enzyme from the bacterium Rhodococcus ruber prefers linear secondary-alkyl sulfate esters, particularly octan-2-yl, octan-3-yl, and octan-4-yl sulfates [1]. The enzyme from the bacterium Pseudomonas sp. DSM6611 utilizes a range of secondary-alkyl sulfate esters bearing aromatic, olefinic and acetylenic moieties. Hydrolysis proceeds through inversion of the configuration at the stereogenic carbon atom, resulting in perfect enantioselectivity. cf. EC 3.1.6.1, arylsulfatase (type I), and EC 1.14.11.77, alkyl sulfatase (type II).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Pogorevc, M. and Faber, K. Purification and characterization of an inverting stereo- and enantioselective sec-alkylsulfatase from the gram-positive bacterium Rhodococcus ruber DSM 44541. Appl. Environ. Microbiol. 69 (2003) 2810-2815. [PMID: 12732552]
2. Wallner, S.R., Nestl, B.M. and Faber, K. Highly enantioselective sec-alkyl sulfatase activity of Sulfolobus acidocaldarius DSM 639. Org. Lett. 6 (2004) 5009-5010. [PMID: 15606122]
3. Knaus, T., Schober, M., Kepplinger, B., Faccinelli, M., Pitzer, J., Faber, K., Macheroux, P. and Wagner, U. Structure and mechanism of an inverting alkylsulfatase from Pseudomonas sp. DSM6611 specific for secondary alkyl sulfates. FEBS J. 279 (2012) 4374-4384. [PMID: 23061549]
4. Schober, M., Knaus, T., Toesch, M., Macheroux, P., Wagner, U. and Faber, K. The substrate spectrum of the inverting sec-alkylsulfatase Pisa1. Adv. Synth. Catal. 354 (2012) 1737-1742.
Accepted name: linear primary-alkylsulfatase
Reaction: a primary alkyl sulfate ester + H2O = an alcohol + sulfate
Other name(s): sdsA1 (gene name); yjcS (gene name); type III linear primary-alkylsulfatase
Systematic name: primary alkyl sulfate ester sulfohydrolase
Comments: Sulfatase enzymes are classified as type I, in which the key catalytic residue is 3-oxo-L-alanine, type II, which are non-heme iron-dependent dioxygenases, or type III, whose catalytic domain adopts a metallo-β-lactamase fold and binds two zinc ions as cofactors. This enzyme belongs to the type III sulfatase family. The enzyme is active against linear primary-alkyl sulfate esters, such as dodecyl sulfate, decyl sulfate, octyl sulfate, and hexyl sulfate. It The enzyme from Pseudomonas aeruginosa is secreted out of the cell. The catalytic mechanism begins with activation of a water molecule by the binuclear Zn2+ cluster, resulting in a nucleophilic attack on the carbon atom. cf. EC 3.1.6.22, branched primary-alkylsulfatase, and EC 3.1.6.19, (R)-specific secondary-alkylsulfatase.
References:
1. Hagelueken, G., Adams, T.M., Wiehlmann, L., Widow, U., Kolmar, H., Tummler, B., Heinz, D.W. and Schubert, W.D. The crystal structure of SdsA1, an alkylsulfatase from Pseudomonas aeruginosa, defines a third class of sulfatases. Proc. Natl. Acad. Sci. USA 103 (2006) 7631-7636. [PMID: 16684886]
2. Long, M., Ruan, L., Li, F., Yu, Z. and Xu, X. Heterologous expression and characterization of a recombinant thermostable alkylsulfatase (sdsAP). Extremophiles 15 (2011) 293-301. [PMID: 21318560]
3. Liang, Y., Gao, Z., Dong, Y. and Liu, Q. Structural and functional analysis show that the Escherichia coli uncharacterized protein YjcS is likely an alkylsulfatase. Protein Sci. 23 (2014) 1442-1450. [PMID: 25066955]
4. Sun, L., Chen, P., Su, Y., Cai, Z., Ruan, L., Xu, X. and Wu, Y. Crystal structure of thermostable alkylsulfatase SdsAP from Pseudomonas sp. S9. Biosci Rep 37 (2017) . [PMID: 28442601]
Accepted name: branched primary-alkylsulfatase
Reaction: 2-butyloctyl sulfate + H2O = 2-butyloctan-1-ol + sulfate
Other name(s): DP1 (gene name); type III branched primary-alkylsulfatase
Systematic name: branched primary-alkyl sulfate ester sulfohydrolase
Comments: Sulfatase enzymes are classified as type I, in which the key catalytic residue is 3-oxo-L-alanine, type II, which are non-heme iron-dependent dioxygenases, or type III, whose catalytic domain adopts a metallo-β-lactamase fold and binds two zinc ions as cofactors. This enzyme belongs to the type III family. The enzyme, characterized from a Pseudomonas strain, is specific for branched primary-alkyl sulfate esters and does not act on linear substrates such as dodecyl sulfate. cf. EC 3.1.6.1, arylsulfatase (type I), EC 1.14.11.77, alkyl sulfatase, EC 3.1.6.19, (R)-specific secondary-alkylsulfatase (type III) and EC 3.1.6.21, linear primary-alkylsulfatase.
References:
1. Ellis, A.J., Hales, S.G., Ur-Rehman, N.G. and White, G.F. Novel alkylsulfatases required for biodegradation of the branched primary alkyl sulfate surfactant 2-butyloctyl sulfate. Appl. Environ. Microbiol. 68 (2002) 31-36. [PMID: 11772605]
2. Toesch, M., Schober, M. and Faber, K. Microbial alkyl- and aryl-sulfatases: mechanism, occurrence, screening and stereoselectivities. Appl. Microbiol. Biotechnol. 98 (2014) 1485-1496. [PMID: 24352732]
Accepted name: crossover junction endodeoxyribonuclease
Reaction: Endonucleolytic cleavage at a junction such as a reciprocal single-stranded crossover between two homologous DNA duplexes (Holliday junction)
Other name(s): Hje endonuclease; Holliday junction endonuclease CCE1; Holliday junction resolvase; Holliday junction-cleaving endonuclease; Holliday junction-resolving endoribonuclease; RusA Holliday junction resolvase; RusA endonuclease; RuvC endonuclease; SpCCe1 Holliday junction resolvase; crossover junction endoribonuclease; cruciform-cutting endonuclease; endo X3; endonuclease RuvC; endonuclease VII; endonuclease X3; resolving enzyme CCE1
Comments: The enzyme from Saccharomyces cerevisiae has no endonuclease or exonuclease activity on single-stranded or double-stranded DNA molecules that do not contain Holliday junctions.
References:
1. Symington, L.S. and Kolodner, R. Partial purification of an enzyme from Saccharomyces cerevisiae that cleaves Holliday junctions. Proc. Natl. Acad. Sci. USA 82 (1985) 7247-7251. [PMID: 3903750]
2. Shida, T., Iwasaki, H., Saito, A., Kyogoku, Y. and Shinagawa, H. Analysis of substrate specificity of the RuvC holliday junction resolvase with synthetic Holliday junctions. J. Biol. Chem. 271 (1996) 26105-26109. [PMID: 8824253]
3. Shah, R., Cosstick, R. and West, S.C. The RuvC protein dimer resolves Holliday junctions by a dual incision mechanism that involves base-specific contacts. EMBO J. 16 (1997) 1464-1472. [PMID: 9135161]
4. Fogg, J.M., Schofield, M.J., White, M.F. and Lilley, D.M. Sequence and functional-group specificity for cleavage of DNA junctions by RuvC of Escherichia coli. Biochemistry 38 (1999) 11349-11358. [PMID: 10471285]
5. Lilley, D.M. and White, M.F. The junction-resolving enzymes. Nat. Rev. Mol. Cell. Biol. 2 (2001) 433-443. [PMID: 11389467]
6. Middleton, C.L., Parker, J.L., Richard, D.J., White, M.F. and Bond, C.S. Crystallization and preliminary X-ray diffraction studies of Hje, a Holliday junction resolving enzyme from Sulfolobus solfataricus. Acta Crystallogr. D Biol. Crystallogr. 59 (2003) 171-173. [PMID: 12499561]
[EC 3.1.22.4 Transferred entry: crossover junction endodeoxyribonuclease. Now EC 3.1.21.10, crossover junction endodeoxyribonuclease (EC 3.1.22.4 created 1989, modified 2003, deleted 2021)]
[EC 3.2.1.47 Deleted entry: galactosylgalactosylglucosylceramidase. Now known to be catalyzed by EC 3.2.1.22, α-galactosidase. (EC 3.2.1.47 created 1972, modified 2011, deleted 2021)]
Accepted name: [mycofactocin precursor peptide] peptidase
Reaction: C-terminal [mycofactocin precursor peptide]-glycyl-3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one + H2O = C-terminal [mycofactocin precursor peptide]-glycine + 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one
Glossary: 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one = AHDP
Other name(s): mftE (gene name)
Systematic name: C-terminal [mycofactocin precursor peptide]-glycyl-3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one hydrolyase
Comments: Requires Fe2+ ad Zn2+. The enzyme participates in the biosynthesis of the enzyme cofactor mycofactocin. It catalyses cleavage of the mycofactocin precursor peptide following its modification by MftC to liberate its final two residues, which consist of a cross-linked valine-tyramine dipeptide.
References:
1. Bruender, N.A. and Bandarian, V. The creatininase homolog MftE from Mycobacterium smegmatis catalyzes a peptide cleavage reaction in the biosynthesis of a novel ribosomally synthesized post-translationally modified peptide (RiPP). J. Biol. Chem. 292 (2017) 4371-4381. [PMID: 28077628]
2. Ayikpoe, R., Salazar, J., Majestic, B. and Latham, J.A. Mycofactocin biosynthesis proceeds through 3-amino-5-[(p-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone (AHDP); direct observation of MftE specificity toward MftA. Biochemistry 57 (2018) 5379-5383. [PMID: 30183269]
Accepted name: 3-oxoisoapionate-4-phosphate transcarboxylase/hydrolase
Reaction: 3-oxoisoapionate 4-phosphate + H2O = glycolate + 3-phospho-D-glycerate
Glossary: 3-oxoisoapionate = 2,4-dihydroxy-2-(hydroxymethyl)-3-oxobutanoate
Other name(s): oiaT (gene name)
Systematic name: 3-oxoisoapionate-4-phosphate transcarboxylase/glycolylhydrolase (3-phospho-D-glycerate-forming)
Comments: The enzyme, which belongs to the RuBisCO-like-protein (RLP) superfamily, has been characterized from several bacterial species. It participates in the degradation of D-apionate. The reaction is initiated by decarboxylation to generate a stabilized enediolate intermediate, with the sequestered CO2 carboxylating the adjacent enediolate carbon atom. The resulting 3-ketose-1-phosphate intermediate is hydrolysed, as in the authentic RuBisCO-catalysed reaction, to generate glycolate and 3-phospho-D-glycerate. Stereospecificity of 3-oxoisoapionate 4-phosphate has not been determined.
References:
1. Carter, M.S., Zhang, X., Huang, H., Bouvier, J.T., Francisco, B.S., Vetting, M.W., Al-Obaidi, N., Bonanno, J.B., Ghosh, A., Zallot, R.G., Andersen, H.M., Almo, S.C. and Gerlt, J.A. Functional assignment of multiple catabolic pathways for D-apiose. Nat. Chem. Biol. 14 (2018) 696-705. [PMID: 29867142]
Accepted name: 2-hydroxyacyl-CoA lyase
Reaction: (1) a 2-hydroxy-3-methyl-Cn-fatty-acyl-CoA = a 2-methyl-branched Cn-1-fatty aldehyde + formyl-CoA
(2) a (2R)-2-hydroxy-Cn-long-chain fatty acyl-CoA = a Cn-1-long-chain fatty aldehyde + formyl-CoA
Other name(s): HACL1 (gene name); 2-hydroxyphytanoyl-CoA lyase; 2-HPCL
Systematic name: 2-hydroxy-3-methyl fatty-CoA formyl-CoA lyase (2-methyl branched fatty aldehyde-forming)
Comments: Requires Mg2+ and thiamine diphosphate. This peroxisomal enzyme, found in animals, is involved in the α-oxidation of 3-methyl-branched fatty acids like phytanic acid and the shortening of 2-hydroxy long-chain fatty acids.
References:
1. Foulon, V., Antonenkov, V.D., Croes, K., Waelkens, E., Mannaerts, G.P., Van Veldhoven, P.P. and Casteels, M. Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during α-oxidation of 3-methyl-branched fatty acids. Proc. Natl. Acad. Sci. USA 96 (1999) 10039-10044. [PMID: 10468558]
2. Foulon, V., Sniekers, M., Huysmans, E., Asselberghs, S., Mahieu, V., Mannaerts, G.P., Van Veldhoven, P.P. and Casteels, M. Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the α-oxidation of straight chain fatty acids. J. Biol. Chem. 280 (2005) 9802-9812. [PMID: 15644336]
3. Casteels, M., Sniekers, M., Fraccascia, P., Mannaerts, G.P. and Van Veldhoven, P.P. The role of 2-hydroxyacyl-CoA lyase, a thiamin pyrophosphate-dependent enzyme, in the peroxisomal metabolism of 3-methyl-branched fatty acids and 2-hydroxy straight-chain fatty acids. Biochem Soc Trans. 35 (2007) 876-880. [PMID: 17956236]
Accepted name: N-acetylneuraminate lyase
Reaction: aceneuramate = N-acetyl-D-mannosamine + pyruvate
Glossary: aceneuramate = (4S,5R,6R,7S,8R)-5-acetamido-4,6,7,8,9-pentahydroxy-2-oxononanoate
Other name(s): N-acetylneuraminic acid aldolase; acetylneuraminate lyase; sialic aldolase; sialic acid aldolase; sialate lyase; N-acetylneuraminic aldolase; neuraminic aldolase; N-acetylneuraminate aldolase; neuraminic acid aldolase; neuraminate aldolase; N-acetylneuraminic lyase; N-acetylneuraminic acid lyase; NPL; NALase; NANA lyase; acetylneuraminate pyruvate-lyase; N-acetylneuraminate pyruvate-lyase; NanA; N-acetylneuraminate pyruvate-lyase (N-acetyl-D-mannosamine-forming)
Systematic name: aceneuramate pyruvate-lyase (N-acetyl-D-mannosamine-forming)
Comments: This enzyme is involved in the degradation of N-acetylneuraminate. It is specific for the open form of the sugar. It also acts on N-glycoloylneuraminate and on O-acetylated sialic acids, other than 4-O-acetylated derivatives.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9027-60-5
References:
1. Comb, D.G. and Roseman, S. The sialic acids. I. The structure and enzymatic synthesis of N-acetylneuraminic acid. J. Biol. Chem. 235 (1960) 2529-2537. [PMID: 13811398]
2. Schauer, R. Sialic acids. Adv. Carbohydr. Chem. Biochem. 40 (1982) 131-234. [PMID: 6762816]
3. Kentache, T., Thabault, L., Deumer, G., Haufroid, V., Frederick, R., Linster, C.L., Peracchi, A., Veiga-da-Cunha, M., Bommer, G.T. and Van Schaftingen, E. The metalloprotein YhcH is an anomerase providing N-acetylneuraminate aldolase with the open form of its substrate. J. Biol. Chem. (2021) 100699. [PMID: 33895133]
Accepted name: L-lyxonate dehydratase
Reaction: L-lyxonate = 2-dehydro-3-deoxy-L-arabinonate + H2O
Glossary: L-lyxonate = (2R,3R,4S)-2,3,4,5-tetrahydroxypentanoate
Other name(s): lyxD (gene name)
Systematic name: L-lyxonate hydro-lyase
Comments: The enzyme, characterized from several bacterial species, is involved in an L-lyxonate degradation pathway.
References:
1. Ghasempur, S., Eswaramoorthy, S., Hillerich, B.S., Seidel, R.D., Swaminathan, S., Almo, S.C. and Gerlt, J.A. Discovery of a novel L-lyxonate degradation pathway in Pseudomonas aeruginosa PAO1. Biochemistry 53 (2014) 3357-3366. [PMID: 24831290]
Accepted name: (2S)-3-sulfopropanediol dehydratase
Reaction: (2S)-2,3-dihydroxypropane-1-sulfonate = 3-oxopropane-1-sulfonate + H2O
Glossary: (2S)-2,3-dihydroxypropane-1-sulfonic acid = (2S)-3-sulfopropanediol = (S)-DHPS
Other name(s): hpfG (gene name); (S)-DHPS dehydratase
Systematic name: (2S)-2,3-dihydroxypropane-1-sulfonate hydro-lyase
Comments: The enzyme, characterized from the bacterium Klebsiella oxytoca, participates in (2S)-2,3-dihydroxypropane-1-sulfonate degradation. The active form of the enzyme contains a glycyl radical that is generated by a dedicated activating enzyme via chemistry involving S-adenosyl-L-methionine (AdoMet) and a [4Fe-4S] cluster.
References:
1. Liu, J., Wei, Y., Lin, L., Teng, L., Yin, J., Lu, Q., Chen, J., Zheng, Y., Li, Y., Xu, R., Zhai, W., Liu, Y., Liu, Y., Cao, P., Ang, E.L., Zhao, H., Yuchi, Z. and Zhang, Y. Two radical-dependent mechanisms for anaerobic degradation of the globally abundant organosulfur compound dihydroxypropanesulfonate. Proc. Natl. Acad. Sci. USA 117 (2020) 15599-15608. [PMID: 32571930]
Accepted name: isethionate sulfite-lyase
Reaction: isethionate = acetaldehyde + sulfite
Glossary: isethionate = 2-hydroxyethanesulfonate
Other name(s): islA (gene name)
Systematic name: isethionate sulfite-lyase
Comments: The enzyme, characterized from the human gut bacterium Bilophila wadsworthia, participates in a taurine degradation pathway that leads to sulfide production. The active form of the enzyme contains a glycyl radical that is generated by a dedicated activating enzyme via chemistry involving S-adenosyl-L-methionine (SAM) and a [4Fe-4S] cluster.
References:
1. Peck, S.C., Denger, K., Burrichter, A., Irwin, S.M., Balskus, E.P. and Schleheck, D. A glycyl radical enzyme enables hydrogen sulfide production by the human intestinal bacterium Bilophila wadsworthia. Proc. Natl. Acad. Sci. USA 116 (2019) 3171-3176. [PMID: 30718429]
2. Xing, M., Wei, Y., Zhou, Y., Zhang, J., Lin, L., Hu, Y., Hua, G.,, N. Nanjaraj Urs, A., Liu, D., Wang, F., Guo, C., Tong, Y., Li, M., Liu, Y., Ang, E.L., Zhao, H., Yuchi, Z. and Zhang, Y. Radical-mediated C-S bond cleavage in C2 sulfonate degradation by anaerobic bacteria. Nat. Commun. 10 (2019) 1609. [PMID: 30962433]
Accepted name: C-phycoerythrin α-cysteine-82 phycoerythrobilin lyase
Reaction: a [C-phycoerythrin α-subunit]-Cys82-phycoerythrobilin = apo-[C-phycocyanin α-subunit] + (3E)-phycoerythrobilin
Other name(s): cpeY (gene name)
Systematic name: [C-phycoerythrin α-subunit]-Cys82-phycoerythrobilin:phycoerythrobilin lyase
Comments: The enzyme, characterized from the cyanobacterium Microchaete diplosiphon, catalyses the attachment of the phycobilin chromophore (3E)-phycoerythrobilin (PEB) to cysteine 82 of the α subunit of the phycobiliprotein C-phycoerythrin. The numbering used here corresponds to the enzyme from Microchaete diplosiphon, and could vary slightly in other organisms. Activity is greatly enhanced in the presence of the chaperone-like protein CpeZ. The reaction could also be catalysed by EC 4.4.1.29, phycobiliprotein cysteine-84 phycobilin lyase, but much less efficiently.
References:
1. Biswas, A., Boutaghou, M.N., Alvey, R.M., Kronfel, C.M., Cole, R.B., Bryant, D.A. and Schluchter, W.M. Characterization of the activities of the CpeY, CpeZ, and CpeS bilin lyases in phycoerythrin biosynthesis in Fremyella diplosiphon strain UTEX 481. J. Biol. Chem. 286 (2011) 35509-35521. [PMID: 21865169]
2. Kronfel, C.M., Biswas, A., Frick, J.P., Gutu, A., Blensdorf, T., Karty, J.A., Kehoe, D.M. and Schluchter, W.M. The roles of the chaperone-like protein CpeZ and the phycoerythrobilin lyase CpeY in phycoerythrin biogenesis. Biochim Biophys Acta Bioenerg 1860 (2019) S0005-2728(. [PMID: 31173730]
Accepted name: C-phycoerythrin β-cysteine-48/59 phycoerythrobilin lyase
Reaction: a [C-phycoerythrin β-subunit]-Cys48/59-phycoerythrobilin = apo-[C-phycocyanin α-subunit] + (3E)-phycoerythrobilin
Other name(s): cpeY (gene name)
Systematic name: [C-phycoerythrin β-subunit]-Cys48/59-phycoerythrobilin:phycoerythrobilin lyase
Comments: The enzyme, characterized from the cyanobacterium Microchaete diplosiphon, catalyses the attachment of the phycobilin chromophore (3E)-phycoerythrobilin (PEB) to cysteine 48 and 59 of the β subunits of the phycobiliprotein C-phycoerythrin. The enzyme first ligates the A ring of PEB to cysteine-48, followed by the attachment of the D ring to cysteine-59. The numbering used here corresponds to the enzyme from Microchaete diplosiphon, and could vary slightly in other organisms. The reaction requires the presence of the chaperone-like protein CpeZ.
References:
1. Kronfel, C.M., Hernandez, C.V., Frick, J.P., Hernandez, L.S., Gutu, A., Karty, J.A., Boutaghou, M.N., Kehoe, D.M., Cole, R.B. and Schluchter, W.M. CpeF is the bilin lyase that ligates the doubly linked phycoerythrobilin on β-phycoerythrin in the cyanobacterium Fremyella diplosiphon. J. Biol. Chem. 294 (2019) 3987-3999. [PMID: 30670589]
Accepted name: (2S)-3-sulfopropanediol sulfolyase
Reaction: (2S)-2,3-dihydroxypropane-1-sulfonate = hydroxyacetone + sulfite
Glossary: (2S)-2,3-dihydroxypropane-1-sulfonate = (2S)-3-sulfopropanediol
Other name(s): DHPS sulfolyase; hpsG (gene name)
Systematic name: (2S)-2,3-dihydroxypropane-1-sulfonate sulfite-lyase
Comments: The enzyme, characterized from the human gut bacterium Bilophila wadsworthia, contains a glycyl radical that is generated by a dedicated activating enzyme via chemistry involving S-adenosyl-L-methionine (AdoMet) and a [4Fe-4S] cluster.
References:
1. Liu, J., Wei, Y., Lin, L., Teng, L., Yin, J., Lu, Q., Chen, J., Zheng, Y., Li, Y., Xu, R., Zhai, W., Liu, Y., Liu, Y., Cao, P., Ang, E.L., Zhao, H., Yuchi, Z. and Zhang, Y. Two radical-dependent mechanisms for anaerobic degradation of the globally abundant organosulfur compound dihydroxypropanesulfonate. Proc. Natl. Acad. Sci. USA 117 (2020) 15599-15608. [PMID: 32571930]
Accepted name: N-acetylneuraminate epimerase
Reaction: N-acetyl-α-neuraminate = N-acetyl-β-neuraminate (oveall reaction)
(1a) N-acetyl-α-neuraminate = aceneuramate
(1b) aceneuramate = N-acetyl-β-neuraminate
Glossary: aceneuramate = (4S,5R,6R,7S,8R)-5-acetamido-4,6,7,8,9-pentahydroxy-2-oxononanoate
Other name(s): sialic acid epimerase; N-acetylneuraminate mutarotase; NanM; NanQ
Systematic name: N-acetyl-α-neuraminate 2-epimerase
Comments: Sialoglycoconjugates present in vertebrates are linked exclusively by α-linkages and are released in α form during degradation. This enzyme accelerates maturotation to the β form via the open form (which also occurs as a slow spontaneous reaction). The open form is necessary for further metabolism by the bacteria.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Severi, E., Müller, A., Potts, J.R., Leech, A., Williamson, D., Wilson, K.S. and Thomas, G.H. Sialic acid mutarotation is catalyzed by the Escherichia coli β-propeller protein YjhT. J. Biol. Chem. 283 (2008) 4841-4849. [PMID: 18063573]
2. Kentache, T., Thabault, L., Deumer, G., Haufroid, V., Frederick, R., Linster, C.L., Peracchi, A., Veiga-da-Cunha, M., Bommer, G.T. and Van Schaftingen, E. The metalloprotein YhcH is an anomerase providing N-acetylneuraminate aldolase with the open form of its substrate. J. Biol. Chem. (2021) 100699. [PMID: 33895133]
Accepted name: L-cysteine—[L-cysteinyl-carrier protein] ligase
Reaction: ATP + L-cysteine + holo-[L-cysteinyl-carrier protein] = AMP + diphosphate + L-cysteinyl-[L-cysteinyl-carrier protein] (overall reaction)
(1a) ATP + L-cysteine = diphosphate + (L-cysteinyl)adenylate
(1b) (L-cysteinyl)adenylate + holo-[L-cysteinyl-carrier protein] = AMP + L-cysteinyl-[L-cysteinyl-carrier protein]
Other name(s): pchE (gene name); pchF (gene name); angR (gene name)
Systematic name: L-cysteine:[L-cysteinyl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-cysteine to (L-cysteinyl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of a peptidyl-carrier protein domain. The peptidyl-carrier protein domain may be part of the same protein, or of a different protein. This activity is often found as part of a larger non-ribosomal peptide synthase.
References:
1. Quadri, L.E., Keating, T.A., Patel, H.M. and Walsh, C.T. Assembly of the Pseudomonas aeruginosa nonribosomal peptide siderophore pyochelin: In vitro reconstitution of aryl-4, 2-bisthiazoline synthetase activity from PchD, PchE, and PchF. Biochemistry 38 (1999) 14941-14954. [PMID: 10555976]
Accepted name: L-threonine—[L-threonyl-carrier protein] ligase
Reaction: ATP + L-threonine + holo-[L-threonyl-carrier protein] = AMP + diphosphate + L-threonyl-[L-threonyl-carrier protein] (overall reaction)
(1a) ATP + L-threonine = diphosphate + (L-threonyl)adenylate
(1b) (L-threonyl)adenylate + holo-[L-threonyl-carrier protein] = AMP + L-threonyl-[L-threonyl-carrier protein]
Other name(s): dhbF (gene name); pmsD (gene name); syrB1 (gene name)
Systematic name: L-threonine:[L-threonyl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-threonine to (L-threonyl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of a peptidyl-carrier protein domain. The peptidyl-carrier protein domain may be part of the same protein (as in the case of DhbF in bacillibactin biosynthesis), or of a different protein (as in the case of PmsD in pseudomonine biosynthesis). This activity is often found as part of a larger non-ribosomal peptide synthase.
References:
1. Vaillancourt, F.H., Yin, J. and Walsh, C.T. SyrB2 in syringomycin E biosynthesis is a nonheme FeII α-ketoglutarate- and O2-dependent halogenase. Proc. Natl. Acad. Sci. USA 102 (2005) 10111-10116. [PMID: 16002467]
2. Sattely, E.S. and Walsh, C.T. A latent oxazoline electrophile for N-O-C bond formation in pseudomonine biosynthesis. J. Am. Chem. Soc. 130 (2008) 12282-12284. [PMID: 18710233]
Accepted name: 2,3-dihydroxybenzoate—[aryl-carrier protein] ligase
Reaction: ATP + 2,3-dihydroxybenzoate + holo-[aryl-carrier protein] = AMP + diphosphate + 2,3-dihydroxybenzoyl-[aryl-carrier protein] (overall reaction)
(1a) ATP + 2,3-dihydroxybenzoate = diphosphate + (2,3-dihydroxybenzoyl)adenylate
(1b) (2,3-dihydroxybenzoyl)adenylate + holo-[aryl-carrier protein] = AMP + 2,3-dihydroxybenzoyl-[aryl-carrier protein]
Other name(s): entE (gene name); vibE (gene name); dhbE (gene name); angE (gene name)
Systematic name: 2,3-dihydroxybenzoate:[aryl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of 2,3-dihydroxybenzoate to (2,3-dihydroxybenzoyl)adenylate, followed by the transfer the activated compound to the free thiol of a phosphopantetheine arm of an aryl-carrier protein domain of a specific non-ribosomal peptide synthase. For example, the EntE enzyme of Escherichia coli is part of the enterobactin synthase complex, the VibE enzyme of Vibrio cholerae is part of the vibriobactin synthase complex, and the DhbE enzyme of Bacillus subtilis is part of the bacillibactin synthase complex.
References:
1. Gehring, A.M., Bradley, K.A. and Walsh, C.T. Enterobactin biosynthesis in Escherichia coli: isochorismate lyase (EntB) is a bifunctional enzyme that is phosphopantetheinylated by EntD and then acylated by EntE using ATP and 2,3-dihydroxybenzoate. Biochemistry 36 (1997) 8495-8503. [PMID: 9214294]
2. Wyckoff, E.E., Stoebner, J.A., Reed, K.E. and Payne, S.M. Cloning of a Vibrio cholerae vibriobactin gene cluster: identification of genes required for early steps in siderophore biosynthesis. J. Bacteriol. 179 (1997) 7055-7062. [PMID: 9371453]
3. Ehmann, D.E., Shaw-Reid, C.A., Losey, H.C. and Walsh, C.T. The EntF and EntE adenylation domains of Escherichia coli enterobactin synthetase: sequestration and selectivity in acyl-AMP transfers to thiolation domain cosubstrates. Proc. Natl. Acad. Sci. USA 97 (2000) 2509-2514. [PMID: 10688898]
4. Keating, T.A., Marshall, C.G. and Walsh, C.T. Vibriobactin biosynthesis in Vibrio cholerae: VibH is an amide synthase homologous to nonribosomal peptide synthetase condensation domains. Biochemistry 39 (2000) 15513-15521. [PMID: 11112537]
5. May, J.J., Wendrich, T.M. and Marahiel, M.A. The dhb operon of Bacillus subtilis encodes the biosynthetic template for the catecholic siderophore 2,3-dihydroxybenzoate-glycine-threonine trimeric ester bacillibactin. J. Biol. Chem. 276 (2001) 7209-7217. [PMID: 11112781]
6. Sikora, A.L., Wilson, D.J., Aldrich, C.C. and Blanchard, J.S. Kinetic and inhibition studies of dihydroxybenzoate-AMP ligase from Escherichia coli. Biochemistry 49 (2010) 3648-3657. [PMID: 20359185]
7. Khalil, S. and Pawelek, P.D. Enzymatic adenylation of 2,3-dihydroxybenzoate is enhanced by a protein-protein interaction between Escherichia coli 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase (EntA) and 2,3-dihydroxybenzoate-AMP ligase (EntE). Biochemistry 50 (2011) 533-545. [PMID: 21166461]
Accepted name: L-serine—[L-seryl-carrier protein] ligase
Reaction: ATP + L-serine + holo-[L-seryl-carrier protein] = AMP + diphosphate + L-seryl-[L-seryl-carrier protein] (overall reaction)
(1a) ATP + L-serine = diphosphate + (L-seryl)adenylate
(1b) (L-seryl)adenylate + holo-[L-seryl-carrier protein] = AMP + L-seryl-[L-seryl-carrier protein]
Other name(s): entF (gene name); zmaJ (gene name); gdnB (gene name); serine-activating enzyme
Systematic name: L-serine:[L-seryl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-serine to (L-seryl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of a peptidyl-carrier protein domain. The peptidyl-carrier protein domain may be part of the same protein, or of a different protein. This activity is often found as part of a larger non-ribosomal peptide synthase.
References:
1. Pettis, G.S. and McIntosh, M.A. Molecular characterization of the Escherichia coli enterobactin cistron entF and coupled expression of entF and the fes gene. J. Bacteriol. 169 (1987) 4154-4162. [PMID: 3040679]
2. Rusnak, F., Sakaitani, M., Drueckhammer, D., Reichert, J. and Walsh, C.T. Biosynthesis of the Escherichia coli siderophore enterobactin: sequence of the entF gene, expression and purification of EntF, and analysis of covalent phosphopantetheine. Biochemistry 30 (1991) 2916-2927. [PMID: 1826089]
3. Reichert, J., Sakaitani, M. and Walsh, C.T. Characterization of EntF as a serine-activating enzyme. Protein Sci. 1 (1992) 549-556. [PMID: 1338974]
4. Ehmann, D.E., Shaw-Reid, C.A., Losey, H.C. and Walsh, C.T. The EntF and EntE adenylation domains of Escherichia coli enterobactin synthetase: sequestration and selectivity in acyl-AMP transfers to thiolation domain cosubstrates. Proc. Natl. Acad. Sci. USA 97 (2000) 2509-2514. [PMID: 10688898]
5. 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]
6. Frueh, D.P., Arthanari, H., Koglin, A., Vosburg, D.A., Bennett, A.E., Walsh, C.T. and Wagner, G. Dynamic thiolation-thioesterase structure of a non-ribosomal peptide synthetase. Nature 454 (2008) 903-906. [PMID: 18704088]
Accepted name: L-tryptophan—[L-tryptophyl-carrier protein] ligase
Reaction: ATP + L-tryptophan + holo-[L-tryptophyl-carrier protein] = AMP + diphosphate + -L-tryptophyl-[L-tryptophyl-carrier protein] (overall reaction)
(1a) ATP + tryptophan = diphosphate + (L-tryptophyl)adenylate
(1b) (L-tryptophyl)adenylate + holo-[L-tryptophyl-carrier protein] = AMP + L-tryptophyl-[L-tryptophyl-carrier protein]
Other name(s): ecm13 (gene name); swb11 (gene name)
Systematic name: L-tryptophan:[L-tryptophyl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-tryptophan to (L-tryptophyl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of a peptidyl-carrier protein domain. The peptidyl-carrier protein domain may be part of the same protein, or of a different protein. This activity is often found as part of a larger non-ribosomal peptide synthase.
References:
1. Zhang, C., Kong, L., Liu, Q., Lei, X., Zhu, T., Yin, J., Lin, B., Deng, Z. and You, D. In vitro characterization of echinomycin biosynthesis: formation and hydroxylation of L-tryptophanyl-S-enzyme and oxidation of (2S,3S) β-hydroxytryptophan. PLoS One 8 (2013) e56772. [PMID: 23437232]
Accepted name: 3-amino-5-hydroxybenzoate—[acyl-carrier protein] ligase
Reaction: ATP + 3-amino-5-hydroxybenzoate + a holo-[acyl-carrier protein] = 3-amino-5-hydroxybenzoyl-[acyl-carrier protein] + AMP + diphosphate
Other name(s): rifA (gene name); mitE (gene name)
Systematic name: 3-amino-5-hydroxybenzoate:[acyl carrier protein] ligase (AMP-forming)
Comments: During the biosynthesis of most ansamycin antibiotics such as rifamycins, streptovaricins, naphthomycins, and chaxamycins, the activity is catalysed by the loading domain of the respective polyketide synthase (PKS), which transfers the substrate to the acyl-carrier protein domain of the first extension module of the PKS. During the biosynthesis of the mitomycins the reaction is catalysed by the MitE protein, which transfers the substrate to a dedicated acyl-carrier protein (MmcB).
References:
1. Admiraal, S.J., Walsh, C.T. and Khosla, C. The loading module of rifamycin synthetase is an adenylation-thiolation didomain with substrate tolerance for substituted benzoates. Biochemistry 40 (2001) 6116-6123. [PMID: 11352749]
2. Admiraal, S.J., Khosla, C. and Walsh, C.T. The loading and initial elongation modules of rifamycin synthetase collaborate to produce mixed aryl ketide products. Biochemistry 41 (2002) 5313-5324. [PMID: 11955082]
3. Admiraal, S.J., Khosla, C. and Walsh, C.T. A Switch for the transfer of substrate between nonribosomal peptide and polyketide modules of the rifamycin synthetase assembly line. J. Am. Chem. Soc. 125 (2003) 13664-13665. [PMID: 14599196]
4. Chamberland, S., Gruschow, S., Sherman, D.H. and Williams, R.M. Synthesis of potential early-stage intermediates in the biosynthesis of FR900482 and mitomycin C. Org. Lett. 11 (2009) 791-794. [PMID: 19161340]
Accepted name: 2-amino-2'-deoxyadenylo-succinate synthase
Reaction: ATP + dGMP + L-aspartate = ADP + phosphate + 2-amino-2'-deoxy-N6-[(2S)-succino]adenylate
Glossary: dZTP = 2-amino-2'-deoxyadenosine 5'-triphosphate
Other name(s): purZ (gene name)
Systematic name: dGMP:L-aspartate ligase (ADP-forming)
Comments: The enzyme, characterized from a number of bacteriophages, participates in the biosynthesis of dZTP, which replaces dATP in the genome of these phages.
References:
1. Zhou, Y., Xu, X., Wei, Y., Cheng, Y., Guo, Y., Khudyakov, I., Liu, F., He, P., Song, Z., Li, Z., Gao, Y., Ang, E.L., Zhao, H., Zhang, Y. and Zhao, S. A widespread pathway for substitution of adenine by diaminopurine in phage genomes. Science 372 (2021) 512-516. [PMID: 33926954]
2. Sleiman, D., Garcia, P.S., Lagune, M., Loc'h, J., Haouz, A., Taib, N., Rothlisberger, P., Gribaldo, S., Marliere, P. and Kaminski, P.A. A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes. Science 372 (2021) 516-520. [PMID: 33926955]
Accepted name: ferredoxin—NAD+ oxidoreductase (H+-transporting)
Reaction: 2 reduced ferredoxin [iron-sulfur] cluster + NAD+ + H+ + 2 H+[side 1] = 2 oxidized ferredoxin [iron-sulfur] cluster + NADH + 2 H+[side 2]
Other name(s): Rnf complex (ambiguous); H+-translocating ferredoxin:NAD+ oxidoreductase
Systematic name: ferredoxin:NAD+ oxidoreductase (H+-transporting)
Comments: This iron-sulfur and flavin-containing electron transport complex, isolated from some anaerobic bacteria, couples the energy from reduction of NAD+ by ferredoxin to pumping protons out of the cell, generating a proton motive force across the cytoplasmic membrane. Most similar complexes pump sodium ions rather than protons [cf. EC 7.2.1.2, ferredoxin—NAD+ oxidoreductase (Na+-transporting)].
References:
1. Tremblay, P.L., Zhang, T., Dar, S.A., Leang, C. and Lovley, D.R. The Rnf complex of Clostridium ljungdahlii is a proton-translocating ferredoxin:NAD+ oxidoreductase essential for autotrophic growth. mBio 4 (2012) e00406. [PMID: 23269825]
2. Wang, L., Bradstock, P., Li, C., McInerney, M.J. and Krumholz, L.R. The role of Rnf in ion gradient formation in Desulfovibrio alaskensis. PeerJ 4 (2016) e1919. [PMID: 27114876]
Accepted name: Na+-exporting diphosphatase
Reaction: diphosphate + H2O + Na+[side 1] = 2 phosphate + Na+[side 2]
Other name(s): Na+-translocating membrane pyrophosphatase; sodium-translocating pyrophosphatase
Systematic name: diphosphate phosphohydrolase (Na+-transporting)
Comments: Requires Na+ and K+. This enzyme, found in some bacteria and archaea, couples the energy from diphosphate hydrolysis to active sodium translocation across the membrane. The enzyme is electrogenic, as the Na+ transport results in generation of a positive potential in the inner side of the membrane.
References:
1. Belogurov, G.A., Malinen, A.M., Turkina, M.V., Jalonen, U., Rytkonen, K., Baykov, A.A. and Lahti, R. Membrane-bound pyrophosphatase of Thermotoga maritima requires sodium for activity. Biochemistry 44 (2005) 2088-2096. [PMID: 15697234]
2. Malinen, A.M., Belogurov, G.A., Baykov, A.A. and Lahti, R. Na+-pyrophosphatase: a novel primary sodium pump. Biochemistry 46 (2007) 8872-8878. [PMID: 17605473]
3. Luoto, H.H., Belogurov, G.A., Baykov, A.A., Lahti, R. and Malinen, A.M. Na+-translocating membrane pyrophosphatases are widespread in the microbial world and evolutionarily precede H+-translocating pyrophosphatases. J. Biol. Chem. 286 (2011) 21633-21642. [PMID: 21527638]