Continued from EC 6.1.1
Accepted name: acetate—CoA ligase
Reaction: ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA
Other name(s): acetyl-CoA synthetase; acetyl activating enzyme; acetate thiokinase; acyl-activating enzyme; acetyl coenzyme A synthetase; acetic thiokinase; acetyl CoA ligase; acetyl CoA synthase; acetyl-coenzyme A synthase; short chain fatty acyl-CoA synthetase; short-chain acyl-coenzyme A synthetase; ACS
Systematic name: acetate:CoA ligase (AMP-forming)
Comments: Also acts on propanoate and propenoate.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9012-31-1
References:
1. Chou, T.C. and Lipmann, F. Separation of acetyl transfer enzymes in pigeon liver extract. J. Biol. Chem. 196 (1952) 89-103.
2. Eisenberg, M.A. The acetate-activating enzyme of Rhodospirillum rubrum. Biochim. Biophys. Acta 16 (1955) 58-65.
3. Hele, P. The acetate activating enzyme of beef heart. J. Biol. Chem. 206 (1954) 671-676.
4. Millerd, A. and Bonner, J. Acetate activation and acetoacetate formation in plant systems. Arch. Biochem. Biophys. 49 (1954) 343-355.
Accepted name: medium-chain acyl-CoA ligase
Reaction: ATP + a medium-chain fatty acid + CoA = AMP + diphosphate + a medium-chain acyl-CoA
Other name(s): fadK (gene name); lvaE (gene name); butyryl-CoA synthetase; fatty acid thiokinase (medium chain); acyl-activating enzyme; fatty acid elongase; fatty acid activating enzyme; fatty acyl coenzyme A synthetase; butyrate—CoA ligase; butyryl-coenzyme A synthetase; L-(+)-3-hydroxybutyryl CoA ligase; short-chain acyl-CoA synthetase; medium-chain acyl-CoA synthetase; butanoate:CoA ligase (AMP-forming)
Systematic name: medium-chain fatty acid:CoA ligase (AMP-forming)
Comments: Acts on fatty acids from C4 to C11 and on the corresponding 3-hydroxy and 2,3- or 3,4-unsaturated acids. The enzyme from the bacterium Pseudomonas putida also acts on 4-oxo and 4-hydroxy derivatives.
Links to other databases: BRENDA, EXPASY, ExplorEnz, GTD, , KEGG, MetaCyc, PDB, CAS registry number: 9080-51-7
References:
1. Mahler, H.R., Wakil, S.J. and Bock, R.M. Studies on fatty acid oxidation. I. Enzymatic activation of fatty acids. J. Biol. Chem. 204 (1953) 453-468. [PMID: 13084616]
2. Massaro, E.J. and Lennarz, W.J. The partial purification and characterization of a bacterial fatty acyl coenzyme A synthetase. Biochemistry 4 (1965) 85-90. [PMID: 14285249]
3. Websterlt, J.R., Gerowin, L.D. and Rakita, L. Purification and characteristics of a butyryl coenzyme A synthetase from bovine heart mitochondria. J. Biol. Chem. 240 (1965) 29-33. [PMID: 14253428]
4. Morgan-Kiss, R.M. and Cronan, J.E. The Escherichia coli fadK (ydiD) gene encodes an anerobically regulated short chain acyl-CoA synthetase. J. Biol. Chem. 279 (2004) 37324-37333. [PMID: 15213221]
5. Rand, J.M., Pisithkul, T., Clark, R.L., Thiede, J.M., Mehrer, C.R., Agnew, D.E., Campbell, C.E., Markley, A.L., Price, M.N., Ray, J., Wetmore, K.M., Suh, Y., Arkin, A.P., Deutschbauer, A.M., Amador-Noguez, D. and Pfleger, B.F. A metabolic pathway for catabolizing levulinic acid in bacteria. Nat Microbiol 2 (2017) 1624-1634. [PMID: 28947739]
Accepted name: long-chain-fatty-acid—CoA ligase
Reaction: ATP + a long-chain carboxylate + CoA = AMP + diphosphate + an acyl-CoA
Other name(s): acyl-CoA synthetase; fatty acid thiokinase (long chain); acyl-activating enzyme; palmitoyl-CoA synthase; lignoceroyl-CoA synthase; arachidonyl-CoA synthetase; acyl coenzyme A synthetase; acyl-CoA ligase; palmitoyl coenzyme A synthetase; thiokinase; palmitoyl-CoA ligase; acyl-coenzyme A ligase; fatty acid CoA ligase; long-chain fatty acyl coenzyme A synthetase; oleoyl-CoA synthetase; stearoyl-CoA synthetase; long chain fatty acyl-CoA synthetase; long-chain acyl CoA synthetase; fatty acid elongase; LCFA synthetase; pristanoyl-CoA synthetase; ACS3; long-chain acyl-CoA synthetase I; long-chain acyl-CoA synthetase II; fatty acyl-coenzyme A synthetase; long-chain acyl-coenzyme A synthetase; FAA1
Systematic name: long-chain fatty acid:CoA ligase (AMP-forming)
Comments: Acts on a wide range of long-chain saturated and unsaturated fatty acids, but the enzymes from different tissues show some variation in specificity. The liver enzyme acts on acids from C6 to C20; that from brain shows high activity up to C24.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9013-18-7
References:
1. Bakken, A.M. and Farstad, M. Identical subcellular distribution of palmitoyl-CoA and arachidonoyl-CoA synthetase activities in human blood platelets. Biochem. J. 261 (1989) 71-76. [PMID: 2528345]
2. Hosaka, K., Mishima, M., Tanaka, T., Kamiryo, T. and Numa, S. Acyl-coenzyme-A synthetase I from Candida lipolytica. Purification, properties and immunochemical studies. Eur. J. Biochem. 93 (1979) 197-203. [PMID: 108099]
3. Nagamatsu, K., Soeda, S., Mori, M. and Kishimoto, Y. Lignoceroyl-coenzyme A synthetase from developing rat brain: partial purification, characterization and comparison with palmitoyl-coenzyme A synthetase activity and liver enzyme. Biochim. Biophys. Acta 836 (1985) 80-88. [PMID: 3161545]
4. Tanaka, T., Hosaka, K., Hoshimaru, M. and Numa, S. Purification and properties of long-chain acyl-coenzyme-A synthetase from rat liver. Eur. J. Biochem. 98 (1979) 165-172. [PMID: 467438]
Accepted name: succinate—CoA ligase (GDP-forming)
Reaction: GTP + succinate + CoA = GDP + phosphate + succinyl-CoA
For diagram of reaction click here.
Other name(s): succinyl-CoA synthetase (GDP-forming); succinyl coenzyme A synthetase (guanosine diphosphate-forming); succinate thiokinase (ambiguous); succinic thiokinase (ambiguous); succinyl coenzyme A synthetase (ambiguous); succinate-phosphorylating enzyme (ambiguous); P-enzyme; SCS (ambiguous); G-STK; succinyl coenzyme A synthetase (GDP-forming); succinyl CoA synthetase (ambiguous)
Systematic name: succinate:CoA ligase (GDP-forming)
Comments: Itaconate can act instead of succinate, and ITP instead of GTP.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9014-36-2
References:
1. Hager, L.P. Succinyl CoA synthetase, in Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds.), The Enzymes, 2nd edn., vol. 6, Academic Press, New York, 1962, pp. 387-399.
2. Kaufman, S., Gilvarg, C., Cori, O. and Ochoa, S. Enzymatic oxidation of α-ketoglutarate and coupled phosphorylation. J. Biol. Chem. 203 (1953) 869-888.
3. Mazumder, R., Sanadi, D.R. and Rodwell, W.V. Purification and properties of hog kidney succinic thiokinase. J. Biol. Chem. 235 (1960) 2546-2550.
4. Sanadi, D.R., Gibson, D.M. and Ayengar, P. Guanosine triphosphate, the primary product of phosphorylation coupled to the breakdown of succinyl coenzyme A. Biochim. Biophys. Acta 14 (1954) 434-436.
Accepted name: succinate—CoA ligase (ADP-forming)
Reaction: ATP + succinate + CoA = ADP + phosphate + succinyl-CoA
For diagram of reaction click here.
Other name(s): uccinyl-CoA synthetase (ADP-forming); succinic thiokinase (ambiguous); succinate thiokinase (ambiguous); succinyl-CoA synthetase (ambiguous); succinyl coenzyme A synthetase (adenosine diphosphate-forming); succinyl coenzyme A synthetase (ambiguous); A-STK (adenin nucleotide-linked succinate thiokinase); STK (ambiguous); A-SCS
Systematic name: succinate:CoA ligase (ADP-forming)
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9080-33-5
References:
1. Hager, L.P. Succinyl CoA synthetase, in Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds.), The Enzymes, 2nd edn., vol. 6, Academic Press, New York, 1962, pp. 387-399.
2. Kaufman, S. Studies on the mechanism of the reaction catalyzed by the phosphorylating enzyme. J. Biol. Chem. 216 (1955) 153-164.
3. Kaufman, S. and Alivasatos, S.G.A. Purification and properties of the phosphorylating enzyme from spinach. J. Biol. Chem. 216 (1955) 141-152.
Accepted name: glutarate—CoA ligase
Reaction: ATP + glutarate + CoA = ADP + phosphate + glutaryl-CoA
Other name(s): glutaryl-CoA synthetase; glutaryl coenzyme A synthetase
Systematic name: glutarate:CoA ligase (ADP-forming)
Comments: GTP or ITP can act instead of ATP.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9023-68-1
References:
1. Menon, G.K.K., Friedman, D.L. and Stern, J.R. Enzymic synthesis of glutaryl-coenzyme A. Biochim. Biophys. Acta 44 (1960) 375-377.
Accepted name: cholate—CoA ligase
Reaction: (1) ATP + cholate + CoA = AMP + diphosphate + choloyl-CoA
(2) ATP + (25R)-3α,7α,12α-trihydroxy-5β-cholestanoate + CoA = AMP + diphosphate + (25R)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA
For diagram click here.
Glossary: cholate = 3α,7α,12α-trihydroxy-5β-cholan-24-oate
trihydroxycoprostanoate = 3α,7α,12α-trihydroxy-5β-cholestan-26-oate
Other name(s): BAL; bile acid CoA ligase; bile acid coenzyme A ligase; choloyl-CoA synthetase; choloyl coenzyme A synthetase; cholic thiokinase; cholate thiokinase; cholic acid:CoA ligase; 3α,7α,12α-trihydroxy-5β-cholestanoyl coenzyme A synthetase; 3α,7α,12α-trihydroxy-5β-cholestanoate-CoA ligase; 3α,7α,12α-trihydroxy-5β-cholestanoate-CoA synthetase; THCA-CoA ligase; 3α,7α,12α-trihydroxy-5β-cholestanate—CoA ligase; 3α,7α,12α-trihydroxy-5β-cholestanate:CoA ligase (AMP-forming); cholyl-CoA synthetase; trihydroxycoprostanoyl-CoA synthetase
Systematic name: cholate:CoA ligase (AMP-forming)
Comments: Requires Mg2+ for activity. The mammalian enzyme is membrane-bound and catalyses the first step in the conjugation of bile acids with amino acids, converting bile acids into their acyl-CoA thioesters. Chenodeoxycholate, deoxycholate, lithocholate and trihydroxycoprostanoate can also act as substrates [7]. The bacterial enzyme is soluble and participates in an anaerobic bile acid 7 α-dehydroxylation pathway [5].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9027-90-1
References:
1. Elliott, W.H. The enzymic activation of cholic acid by guinea-pig-liver microsomes. Biochem. J. 62 (1956) 427-433. [PMID: 13303991]
2. Elliott, W.H. The breakdown of adenosine triphosphate accompanying cholic acid activation by guinea-pig liver microsomes. Biochem. J. 65 (1957) 315-321. [PMID: 13403911]
3. Prydz, K., Kase, B.F., Björkhem, I. and Pedersen, J.I. Subcellular localization of 3α,7α-dihydroxy- and 3α,7α,12α-trihydroxy-5β-cholestanoyl-coenzyme A ligase(s) in rat liver. J. Lipid Res. 29 (1988) 997-1004. [PMID: 3183523]
4. Schepers, L., Casteels, M., Verheyden, K., Parmentier, G., Asselberghs, S., Eyssen, H.J. and Mannaerts, G.P. Subcellular distribution and characteristics of trihydroxycoprostanoyl-CoA synthetase in rat liver. Biochem. J. 257 (1989) 221-229. [PMID: 2521999]
5. Mallonee, D.H., Adams, J.L. and Hylemon, P.B. The bile acid-inducible baiB gene from Eubacterium sp. strain VPI 12708 encodes a bile acid-coenzyme A ligase. J. Bacteriol. 174 (1992) 2065-2071. [PMID: 1551828]
6. Wheeler, J.B., Shaw, D.R. and Barnes, S. Purification and characterization of a rat liver bile acid coenzyme A ligase from rat liver microsomes. Arch. Biochem. Biophys. 348 (1997) 15-24. [PMID: 9390170]
7. Falany, C.N., Xie, X., Wheeler, J.B., Wang, J., Smith, M., He, D. and Barnes, S. Molecular cloning and expression of rat liver bile acid CoA ligase. J. Lipid Res. 43 (2002) 2062-2071. [PMID: 12454267]
Accepted name: oxalate—CoA ligase
Reaction: ATP + oxalate + CoA = AMP + diphosphate + oxalyl-CoA
Other name(s): oxalyl-CoA synthetase; oxalyl coenzyme A synthetase
Systematic name: oxalate:CoA ligase (AMP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37318-57-3
References:
1. Giovanelli, J. Oxalyl-coenzyme A synthetase from pea seeds. Biochim. Biophys. Acta 118 (1966) 124-143. [PMID: 4288975]
Accepted name: malate—CoA ligase
Reaction: ATP + malate + CoA = ADP + phosphate + malyl-CoA
Other name(s): malyl-CoA synthetase; malyl coenzyme A synthetase; malate thiokinase
Systematic name: malate:CoA ligase (ADP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37318-58-4
References:
1. Mue, S., Tuboi, S. and Kikuchi, G. On malyl-coenzyme A synthetase. J. Biochem. (Tokyo) 56 (1964) 545-551.
Accepted name: acid—CoA ligase (GDP-forming)
Reaction: GTP + a carboxylate + CoA = GDP + phosphate + acyl-CoA
Other name(s): acyl-CoA synthetase (GDP-forming); acyl coenzyme A synthetase (guanosine diphosphate forming)
Systematic name: carboxylic acid:CoA ligase (GDP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37318-59-5
References:
1. Rossi, C.R. and Gibson, D.M. Activation of fatty acids by a guanosine triphosphate-specific thiokinase from liver mitochondria. J. Biol. Chem. 239 (1964) 1694-1699. [PMID: 14213337]
Accepted name: biotin—CoA ligase
Reaction: ATP + biotin + CoA = AMP + diphosphate + biotinyl-CoA
Other name(s): biotinyl-CoA synthetase; biotin CoA synthetase; biotinyl coenzyme A synthetase
Systematic name: biotin:CoA ligase (AMP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37318-60-8
References:
1. Christner, J.E., Schlesinger, M.J. and Coon, M.J. Enzymatic activation of biotin. Biotinyl adenylate formation. J. Biol. Chem. 239 (1964) 3997-4005.
Accepted name: 4-coumarate—CoA ligase
Reaction: ATP + 4-coumarate + CoA = AMP + diphosphate + 4-coumaroyl-CoA
For diagram click here.
Glossary:
4-coumarate: 3-(4-hydroxyphenyl)prop-2-enoate
Other name(s): 4-coumaroyl-CoA synthetase; p-coumaroyl CoA ligase; p-coumaryl coenzyme A synthetase; p-coumaryl-CoA synthetase; p-coumaryl-CoA ligase; feruloyl CoA ligase; hydroxycinnamoyl CoA synthetase; 4-coumarate:coenzyme A ligase; caffeolyl coenzyme A synthetase; p-hydroxycinnamoyl coenzyme A synthetase; feruloyl coenzyme A synthetase; sinapoyl coenzyme A synthetase; 4-coumaryl-CoA synthetase; hydroxycinnamate:CoA ligase; p-coumaryl-CoA ligase; p-hydroxycinnamic acid:CoA ligase; 4CL
Systematic name: 4-coumarate:CoA ligase (AMP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37332-51-7
References:
1. Gross, G.G. and Zenk, M.H. Isolation and properties of hydroxycinnamate: CoA ligase from lignifying tissue of Forsythia. Eur. J. Biochem. 42 (1974) 453-459. [PMID: 4364250]
2. Lindl, T., Kreuzaler, F. and Hahlbrock, F. Synthesis of p-coumaroyl coenzyme A with a partially purified p-coumarate:CoA ligase from cell suspension cultures of soybean (Glycine max). Biochim. Biophys. Acta 302 (1973) 457-464. [PMID: 4699252]
Accepted name: acetate—CoA ligase (ADP-forming)
Reaction: ATP + acetate + CoA = ADP + phosphate + acetyl-CoA
Other name(s): acetyl-CoA synthetase (ADP-forming); acetyl coenzyme A synthetase (adenosine diphosphate-forming); acetate thiokinase
Systematic name: acetate:CoA ligase (ADP-forming)
Comments: Also acts on propanoate and, very slowly, on butanoate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 62009-85-2
References:
1. Reeves, R.E., Warren, L.G., Susskind, B. and Lo, H.-S. An energy-conserving pyruvate-to-acetate pathway in Entamoeba histolytica. Pyruvate synthase and a new acetate thiokinase. J. Biol. Chem. 252 (1977) 726-731. [PMID: 13076]
Accepted name: 6-carboxyhexanoate—CoA ligase
Reaction: ATP + 6-carboxyhexanoate + CoA = AMP + diphosphate + 6-carboxyhexanoyl-CoA
Other name(s): 6-carboxyhexanoyl-CoA synthetase; pimelyl-CoA synthetase
Systematic name: 6-carboxyhexanoate:CoA ligase (AMP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 55467-50-0
References:
1. Izumi, Y., Morita, H., Sato, K., Tani, Y. and Ogata, K. Synthesis of biotin-vitamers from pimelic acid and coenzyme A by cell-free extracts of various bacteria. Biochim. Biophys. Acta 264 (1972) 210-213. [PMID: 4623286]
2. Izumi, Y., Morita, H., Tani, Y. and Ogata, K. The pimelyl-CoA synthetase responsible for the first step in biotin biosynthesis by microorganisms. Agric. Biol. Chem. 38 (1974) 2257-2262.
Accepted name: arachidonate—CoA ligase
Reaction: ATP + arachidonate + CoA = AMP + diphosphate + arachidonoyl-CoA
Glossary:
arachidonate: (all-Z)-icosa-5,8,11,14-tetraenoate
Other name(s): arachidonoyl-CoA synthetase
Systematic name: arachidonate:CoA ligase (AMP-forming)
Comments: Not identical with EC 6.2.1.3 long-chain-fatty-acid—CoA ligase. Icosa-8,11,14-trienoate, but not the other long-chain fatty acids, can act in place of arachidonate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 82047-87-8
References:
1. Wilson, D.B., Prescott, S.M. and Majerus, P.W. Discovery of an arachidonoyl coenzyme A synthetase in human platelets. J. Biol. Chem. 257 (1982) 3510-3515. [PMID: 7061494]
Accepted name: acetoacetate—CoA ligase
Reaction: ATP + acetoacetate + CoA = AMP + diphosphate + acetoacetyl-CoA
For diagram click here.
Other name(s): acetoacetyl-CoA synthetase
Systematic name: acetoacetate:CoA ligase (AMP-forming)
Comments: Also acts, more slowly, on L-3-hydroxybutanoate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 39394-62-2
References:
1. Fukui, T., Ito, M. and Tomita, K. Purification and characterization of acetoacetyl-CoA synthetase from Zoogloea ramigera I-16-M. Eur. J. Biochem. 127 (1982) 423-428. [PMID: 7140777]
Accepted name: propionate—CoA ligase
Reaction: ATP + propanoate + CoA = AMP + diphosphate + propanoyl-CoA
Other name(s): propionyl-CoA synthetase
Systematic name: propanoate:CoA ligase (AMP-forming)
Comments: Propenoate can act instead of propanoate. Not identical with EC 6.2.1.1 (acetate—CoA ligase) or EC 6.2.1.2 (butyrate—CoA ligase).
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 55326-49-3
References:
1. Ricks, C.A. and Cook, R.M. Regulation of volatile fatty acid uptake by mitochondrial acyl CoA synthetases of bovine liver. J. Dairy Sci. 64 (1981) 2324-2335. [PMID: 7341659]
Accepted name: citrate—CoA ligase
Reaction: ATP + citrate + CoA = ADP + phosphate + (3S)-citryl-CoA
Glossary
citrate: 2-hydroxypropane-1,2,3-tricarboxylate
Other name(s): citryl-CoA synthetase; citrate:CoA ligase; citrate thiokinase
Systematic name: citrate:CoA ligase (ADP-forming)
Comments: The enzyme is a component of EC 2.3.3.8 ATP citrate synthase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 856428-87-0
References:
1. Lill, U., Schreil, A. and Eggerer, H. Isolation of enzymically active fragments formed by limited proteolysis of ATP citrate lyase. Eur. J. Biochem. 125 (1982) 645-650. [PMID: 6749502]
2. Aoshima, M., Ishii, M. and Igarashi, Y. A novel enzyme, citryl-CoA synthetase, catalysing the first step of the citrate cleavage reaction in Hydrogenobacter thermophilus TK-6. Mol. Microbiol. 52, (2004) 751-761. [PMID: 15101981]
Accepted name: long-chain-fatty-acid—protein ligase
Reaction: ATP + a long-chain fatty acid + [protein]-L-cysteine = AMP + diphosphate + a [protein]-S-(long-chain-acyl)-L-cysteine
Other name(s): luxE (gene name); acyl-protein synthetase; long-chain-fatty-acid—luciferin-component ligase
Systematic name: long-chain-fatty-acid:protein ligase (AMP-forming)
Comments: Together with a transferase component (EC 3.1.2.2/EC 3.1.2.14) and a reductase component (EC 1.2.1.50), this enzyme forms a multienzyme fatty acid reductase complex that produces the long-chain aldehyde substrate of the bacterial luciferase enzyme (EC 1.14.14.3). The enzyme activates free long-chain fatty acids, generated by the action of the transferase component, forming a fatty acyl-AMP intermediate, followed by the transfer of the acyl group to an internal L-cysteine residue. It then transfers the acyl group to EC 1.2.1.50, long-chain acyl-protein thioester reductase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 82657-98-5
References:
1. Riendeau, D., Rodrigues, A. and Meighen, E. Resolution of the fatty acid reductase from Photobacterium phosphoreum into acyl protein synthetase and acyl-CoA reductase activities. Evidence for an enzyme complex. J. Biol. Chem. 257 (1982) 6908-6915. [PMID: 7085612]
2. Rodriguez, A. and Meighen, E. Fatty acyl-AMP as an intermediate in fatty acid reduction to aldehyde in luminescent bacteria. J. Biol. Chem. 260 (1985) 771-774. [PMID: 3968067]
3. Wall, L. and Meighen, E.A. Subunit structure of the fatty-acid reductase complex from Photobacterium phosphoreum. Biochemistry 25 (1986) 4315-4321.
4. Soly, R.R. and Meighen, E.A. Identification of the acyl transfer site of fatty acyl-protein synthetase from bioluminescent bacteria. J. Mol. Biol. 219 (1991) 69-77. [PMID: 2023262]
5. Lin, J.W., Chao, Y.F. and Weng, S.F. Nucleotide sequence and functional analysis of the luxE gene encoding acyl-protein synthetase of the lux operon from Photobacterium leiognathi. Biochem. Biophys. Res. Commun. 228 (1996) 764-773. [PMID: 8941351]
Accepted name: long-chain-fatty-acid—[acyl-carrier-protein] ligase
Reaction: ATP + a long-chain fatty acid + an [acyl-carrier protein] = AMP + diphosphate + a long-chain acyl-[acyl-carrier protein]
Other name(s): acyl-[acyl-carrier-protein] synthetase (ambiguous); acyl-ACP synthetase (ambiguous); stearoyl-ACP synthetase; acyl-acyl carrier protein synthetase (ambiguous); long-chain-fatty-acid:[acyl-carrier-protein] ligase (AMP-forming)
Systematic name: long-chain-fatty-acid:[acyl-carrier protein] ligase (AMP-forming)
Comments: The enzyme ligates long chain fatty acids (with aliphatic chain of 13-22 carbons) to an acyl-carrier protein. Not identical with EC 6.2.1.3 long-chain-fatty-acid—CoA ligase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 77322-37-3
References:
1. Ray, T.K. and Cronan, J.E., Jr. Activation of long chain fatty acids with acyl carrier protein: demonstration of a new enzyme, acyl-acyl carrier protein synthetase, in Escherichia coli. Proc. Natl. Acad. Sci. USA 73 (1976) 4374-4378. [PMID: 794875]
2. Kaczmarzyk, D. and Fulda, M. Fatty acid activation in cyanobacteria mediated by acyl-acyl carrier protein synthetase enables fatty acid recycling. Plant Physiol. 152 (2010) 1598-1610. [PMID: 20061450]
[EC 6.2.1.21 Deleted entry: phenylacetate-CoA ligase. Activity covered by EC 6.2.1.30, phenylacetate—CoA ligase (EC 6.2.1.21 created 1986, deleted 2001)]
Accepted name: [citrate (pro-3S)-lyase] ligase
Reaction: ATP + acetate + holo-[citrate (pro-3S)-lyase] = AMP + diphosphate + acetyl-[citrate (pro-3S)-lyase]
Glossary: citrate = 2-hydroxypropane-1,2,3-tricarboxylate
Other name(s): citrate lyase ligase; citrate lyase synthetase; acetate: SH-[acyl-carrier-protein] enzyme ligase (AMP); acetate:HS-citrate lyase ligase; acetate:citrate-(pro-3S)-lyase(thiol-form) ligase (AMP-forming); acetate:[citrate-(pro-3S)-lyase](thiol-form) ligase (AMP-forming)
Systematic name: acetate:holo-[citrate-(pro-3S)-lyase] ligase (AMP-forming)
Comments: Both this enzyme and EC 2.3.1.49, deacetyl-[citrate-(pro-3S)-lyase] S-acetyltransferase, acetylate and activate EC 4.1.3.6, citrate (pro-3S)-lyase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 52660-22-7
References:
1. Antranikian, G. and Gottschalk, G. Copurification of citrate lyase and citrate lyase ligase from Rhodopseudomonas gelatinosa and subsequent separation of the two enzymes. Eur. J. Biochem. 126 (1982) 43-47. [PMID: 7128585]
2. Antranikian, G., Herzberg, C. and Gottschalk, G. Covalent modification of citrate lyase ligase from Clostridium sphenoides by phosphorylation/dephosphorylation. Eur. J. Biochem. 153 (1985) 413-420. [PMID: 3935436]
3. Quentmeier, A. and Antranikian, G. Characterization of citrate lyase from Clostridium sporosphaeroides. Arch. Microbiol. 141 (1985) 85-90. [PMID: 3994485]
4. Schmellenkamp, H. and Eggerer, H. Mechanism of enzymic acetylation of des-acetyl citrate lyase. Proc. Natl. Acad. Sci. USA 71 (1974) 1987-1991. [PMID: 4365579]
Accepted name: dicarboxylate—CoA ligase
Reaction: ATP + an α,ω-dicarboxylate + CoA = AMP + diphosphate + an ω-carboxyacyl-CoA
Other name(s): carboxylyl-CoA synthetase; dicarboxylyl-CoA synthetase
Systematic name: ω-dicarboxylate:CoA ligase (AMP-forming)
Comments: Acts on dicarboxylic acids of chain length C5 to C16; the best substrate is dodecanedioic acid.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 99332-77-1
References:
1. Vamecq, J., de Hoffmann, E. and van Hoof, F. The microsomal dicarboxylyl-CoA synthetase. Biochem. J. 230 (1985) 683-693. [PMID: 4062873]
Accepted name: phytanate—CoA ligase
Reaction: ATP + phytanate + CoA = AMP + diphosphate + phytanoyl-CoA
Other name(s): phytanoyl-CoA ligase
Systematic name: phytanate:CoA ligase (AMP-forming)
Comments: Not identical with EC 6.2.1.20 long-chain-fatty-acid—[acyl-carrier-protein] ligase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 105238-50-4
References:
1. Muralidharan, F.N. and Muralidharan, V.B. Phytanoyl-CoA ligase activity in rat liver. Biochem. Int. 13 (1986) 123-130. [PMID: 3753503]
Accepted name: benzoate—CoA ligase
Reaction: ATP + benzoate + CoA = AMP + diphosphate + benzoyl-CoA
For diagram of reaction click here.
Other name(s): benzoate—coenzyme A ligase; benzoyl-coenzyme A synthetase; benzoyl CoA synthetase (AMP forming)
Systematic name: benzoate:CoA ligase (AMP-forming)
Comments: Also acts on 2-, 3- and 4-fluorobenzoate, but only very slowly on the corresponding chlorobenzoates.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 95329-17-2
References:
1. Hutber, G.N. and Ribbons, D.W. Involvement of coenzyme-A esters in the metabolism of benzoate and cyclohexanecarboxylate by Rhodopseudomonas palustris. J. Gen. Microbiol. 129 (1983) 2413-2420.
2. Schennen, U., Braun, K. and Knackmuss, H.-J. Anaerobic degradation of 2-fluorobenzoate by benzoate-degrading, denitrifying bacteria. J. Bacteriol. 161 (1985) 321-325. [PMID: 2857161]
Accepted name: o-succinylbenzoate—CoA ligase
Reaction: ATP + 2-succinylbenzoate + CoA = AMP + diphosphate + 4-(2-carboxyphenyl)-4-oxobutanoyl-CoA
For diagram click here.
Glossary: 2-succinylbenzoate = o-succinylbenzoate = 4-(2-carboxyphenyl)-4-oxobutanoate
2-succinylbenzoyl-CoA = o-succinylbenzoyl-CoA = 4-(2-carboxyphenyl)-4-oxobutanoyl-CoA
Other name(s): 2-succinylbenzoyl-coenzyme A synthetase; 2-succinylbenzoate:CoA ligase (AMP-forming)
Systematic name: 2-succinylbenzoate:CoA ligase (AMP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 72506-70-8
References:
1. Heide, L., Arendt, S. and Leistner, E. Enzymatic-synthesis, characterization, and metabolism of the coenzyme-A ester of o-succinylbenzoic acid, an intermediate in menaquinone (vitamin K2) biosynthesis. J. Biol. Chem. 257 (1982) 7396-7400. [PMID: 7045104]
2. Kolkmann, R. and Leistner, E. 4-(2'-Carboxyphenyl)-4-oxobutyryl coenzyme-A ester, an intermediate in vitamin K2 (menaquinone) biosynthesis. Z. Naturforsch. C: Sci. 42 (1987) 1207-1214. [PMID: 2966501]
3. Meganathan, R. and Bentley, R. Menaquinone (vitamin K2) biosynthesis: conversion of o-succinylbenzoic acid to 1,4-dihydroxy-2-naphthoic acid by Mycobacterium phlei enzymes. J. Bacteriol. 140 (1979) 92-98. [PMID: 500558]
Accepted name: 4-hydroxybenzoate—CoA ligase
Reaction: ATP + 4-hydroxybenzoate + CoA = AMP + diphosphate + 4-hydroxybenzoyl-CoA
Other name(s): 4-hydroxybenzoate-CoA synthetase; 4-hydroxybenzoate—coenzyme A ligase (AMP-forming); 4-hydroxybenzoyl coenzyme A synthetase; 4-hydroxybenzoyl-CoA ligase
Systematic name: 4-hydroxybenzoate:CoA ligase (AMP-forming)
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 119699-80-8
References:
1. Merkel, S.M., Eberhard, A.E., Gibson, J. and Harwood, C.S. Involvement of coenzyme A thioesters in anaerobic metabolism of 4-hydroxybenzoate by Rhodopseudomonas palustris. J. Bacteriol. 171 (1989) 1-7. [PMID: 2914844]
Accepted name: 3α,7α-dihydroxy-5β-cholestanate—CoA ligase
Reaction: ATP + (25R)-3α,7α-dihydroxy-5β-cholestan-26-oate + CoA = AMP + diphosphate + (25R)-3α,7α-dihydroxy-5β-cholestanoyl-CoA
For diagram click here.
Other name(s): 3α,7α-dihydroxy-5β-cholestanoyl coenzyme A synthetase; DHCA-CoA ligase; 3α,7α-dihydroxy-5β-cholestanate:CoA ligase (AMP-forming)
Systematic name: (25R)-3α,7α-dihydroxy-5β-cholestan-26-oate:CoA ligase (AMP-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 118732-03-9
References:
1. Prydz, K., Kase, B.F., Bjoerkhem, I. and Pedersen, J.I. Subcellular localization of 3α,7α-dihydroxy- and 3α,7α,12α-trihydroxy-5β-cholestanoyl-coenzyme A ligase(s) in rat liver. J. Lipid Res. 29 (1988) 997-1004. [PMID: 3183523]
[EC 6.2.1.29 Deleted entry: 3α,7α,12α-trihydroxy-5β-cholestanate—CoA ligase. The enzyme is identical to EC 6.2.1.7, cholate—CoA ligase (EC 6.2.1.29 created 1992, deleted 2005)]
Accepted name: phenylacetate—CoA ligase
Reaction: ATP + phenylacetate + CoA = AMP + diphosphate + phenylacetyl-CoA
For diagram of reaction click here.
Other name(s): phenacyl coenzyme A synthetase; phenylacetyl-CoA ligase; PA-CoA ligase; phenylacetyl-CoA ligase (AMP-forming)
Systematic name: phenylacetate:CoA ligase (AMP-forming)
Comments: Also acts, more slowly, on acetate, propanoate and butanoate, but not on hydroxy derivatives of phenylacetate and related compounds.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 57219-71-3
References:
1. Martinez-Blanco, H., Reglero, A., Rodriguez-Asparicio, L.B. and Luengo, J.M. Purification and biochemical characterization of phenylacetyl-CoA ligase from Pseudomonas putida. A specific enzyme for the catabolism of phenylacetic acid. J. Biol. Chem. 265 (1990) 7084-7090. [PMID: 2324116]
Accepted name: 2-furoate—CoA ligase
Reaction: ATP + 2-furoate + CoA = AMP + diphosphate + 2-furoyl-CoA
For diagram of reaction click here.
Glossary
anthranilate = 2-aminobenzoate
Other name(s): 2-furoyl coenzyme A synthetase
Systematic name: 2-furoate:CoA ligase (AMP-forming)
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 122320-08-5
References:
1. Koenig, K. and Andreesen, J.R. Molybdenum involvement in aerobic degradation of 2-furoic acid by Pseudomonas putida FU1. Appl. Environ. Microbiol. 55 (1989) 1829-1834.
Accepted name: anthranilate—CoA ligase
Reaction: ATP + anthranilate + CoA = AMP + diphosphate + anthraniloyl-CoA
For diagram click here.
Glossary: anthraniloyl-CoA = 2-aminobenzoyl-CoA
Other name(s): anthraniloyl coenzyme A synthetase; 2-aminobenzoate—CoA ligase; 2-aminobenzoate—coenzyme A ligase; 2-aminobenzoate coenzyme A ligase
Systematic name: anthranilate:CoA ligase (AMP-forming)
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 112692-58-7
References:
1. Altenschmidt, U., Eckerskorn, C. and Fuchs, G. Evidence that enzymes of a novel aerobic 2-amino-benzoate metabolism in denitrifying Pseudomonas are coded on a small plasmid. Eur. J. Biochem. 194 (1990) 647-653. [PMID: 2176602]
Accepted name: 4-chlorobenzoate—CoA ligase
Reaction: 4-chlorobenzoate + CoA + ATP = 4-chlorobenzoyl-CoA + AMP + diphosphate
Systematic name: 4-chlorobenzoate:CoA ligase
Comments: requires Mg2+. This enzyme is part of the bacterial 2,4-dichlorobenzoate degradation pathway.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 141583-20-2
References:
1. Dunaway-Mariano, D., Babbitt, P.C. On the origins and functions of the enzymes of the 4-chlorobenzoate to 4-hydroxybenzoate converting pathway. Biodegradation 5 (1994) 259-276. [PMID: 7765837]
2. Loffler, F., Muller, R., Lingens, F. Purification and properties of 4-halobenzoate-coenzyme A ligase from Pseudomonas sp. CBS3. Biol. Chem. Hoppe-Seyler 373 (1992) 1001-1007. [PMID: 1418673]
3. Chang, K.H., Liang, P.H., Beck, W., Scholten, J.D., Dunaway-Mariano, D. Isolation and characterization of the three polypeptide components of 4-chlorobenzoate dehalogenase from Pseudomonas sp. strain CBS-3. Biochemistry 31 (1992) 5605-5610. [PMID: 1610806]
Accepted name: trans-feruloyl-CoA synthase
Reaction: ferulic acid + CoA + ATP = feruloyl-CoA + products of ATP breakdown
For diagram of reaction click here.
Other name(s): trans-feruloyl-CoA synthetase; trans-ferulate:CoASH ligase (ATP-hydrolysing); ferulate:CoASH ligase (ATP-hydrolysing)
Systematic name: ferulate:CoA ligase (ATP-hydrolysing)
Comments: Requires Mg2+. It has not yet been established whether AMP + diphosphate or ADP + phosphate are formed in this reaction.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Narbad, A. and Gasson, M.J. Metabolism of ferulic acid via vanillin using a novel CoA-dependent pathway in a newly-isolated strain of Pseudomonas fluorescens. Microbiology 144 (1998) 1397-1405. [PMID: 9611814]
2. Pometto, A.L. and Crawford, D.L. Whole-cell bioconversion of vanillin to vanillic acid by Streptomyces viridosporus. Appl. Environ. Microbiol. 45 (1983) 1582-1585. [PMID: 6870241]
Accepted name: acetate—[acyl-carrier protein] ligase
Reaction: ATP + acetate + an [acyl-carrier protein] = AMP + diphosphate + an acetyl-[acyl-carrier protein]
For diagram of reaction click here
Other name(s): HS-acyl-carrier protein:acetate ligase; [acyl-carrier protein]:acetate ligase; MadH; ACP-SH:acetate ligase
Systematic name: acetate:[acyl-carrier-protein] ligase (AMP-forming)
Comments: This enzyme, from the anaerobic bacterium Malonomonas rubra, is a component of the multienzyme complex EC 7.2.4.4, biotin-dependent malonate decarboxylase. The enzyme uses the energy from hydrolysis of ATP to convert the thiol group of the acyl-carrier-protein-bound 2'-(5-phosphoribosyl)-3'-dephospho-CoA cofactor into its acetyl thioester [2].
Links to other databases: BRENDA, EXPASY, ExplorEnz, IUBMB, KEGG, MetaCyc, CAS registry number:
References:
1. Hilbi, H., Dehning, I., Schink, B. and Dimroth, P. Malonate decarboxylase of Malonomonas rubra, a novel type of biotin-containing acetyl enzyme. Eur. J. Biochem. 207 (1992) 117-123. [PMID: 1628643]
2. Berg, M., Hilbi, H. and Dimroth, P. The acyl carrier protein of malonate decarboxylase of Malonomonas rubra contains 2'-(5"-phosphoribosyl)-3'-dephosphocoenzyme A as a prosthetic group. Biochemistry 35 (1996) 4689-4696. [PMID: 8664258]
3. Berg, M., Hilbi, H. and Dimroth, P. Sequence of a gene cluster from Malonomonas rubra encoding components of the malonate decarboxylase Na+ pump and evidence for their function. Eur. J. Biochem. 245 (1997) 103-115. [PMID: 9128730]
4. Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3-10. [PMID: 11902724]
Accepted name: 3-hydroxypropionyl-CoA synthase
Reaction: 3-hydroxypropanoate + ATP + CoA = 3-hydroxypropanoyl-CoA + AMP + diphosphate
For diagram of reaction click here (another example).
Glossary: 3-hydroxypropanoyl-CoA = 3-hydroxypropionyl-CoA
Other name(s): 3-hydroxypropionyl-CoA synthetase (AMP-forming); 3-hydroxypropionate—CoA ligase; hydroxypropionate:CoA ligase (AMP-forming)
Systematic name: hydroxypropanoate:CoA ligase (AMP-forming)
Comments: Catalyses a step in the 3-hydroxypropanoate/4-hydroxybutanoate cycle, an autotrophic CO2 fixation pathway found in some thermoacidophilic archaea [1,2]. The enzymes from Metallosphaera sedula and Sulfolobus tokodaii can also use propionate, acrylate, acetate, and butanoate as substrates [2], and are thus different from EC 6.2.1.17 (propionate—CoA ligase), which does not accept acetate or butanoate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Berg, I.A., Kockelkorn, D., Buckel, W. and Fuchs, G. A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea. Science 318 (2007) 1782-1786. [PMID: 18079405]
2. Alber, B.E., Kung, J.W. and Fuchs, G. 3-Hydroxypropionyl-coenzyme A synthetase from Metallosphaera sedula, an enzyme involved in autotrophic CO2 fixation. J. Bacteriol. 190 (2008) 1383-1389. [PMID: 18165310]
Accepted name: 3-hydroxybenzoate—CoA ligase
Reaction: ATP + 3-hydroxybenzoate + CoA = AMP + diphosphate + 3-hydroxybenzoyl-CoA
Other name(s): 3-hydroxybenzoyl-CoA synthetase; 3-hydroxybenzoate—coenzyme A ligase (AMP-forming); 3-hydroxybenzoyl coenzyme A synthetase; 3-hydroxybenzoyl-CoA ligase
Systematic name: 3-hydroxybenzoate:CoA ligase (AMP-forming)
Comments: The enzyme works equally well with 4-hydroxybenzoate but shows low activity towards benzoate, 4-aminobenzoate, 3-aminobenzoate, 3-fluorobenzoate, 4-fluorobenzoate, 3-chlorobenzoate, and 4-chlorobenzoate. There is no activity with 3,4-dihydroxybenzoate, 2,3-dihydroxybenzoate, and 2-hydroxybenzoate as substrates.
References:
1. Laempe, D., Jahn, M., Breese, K., Schägger, H. and Fuchs, G. Anaerobic metabolism of 3-hydroxybenzoate by the denitrifying bacterium Thauera aromatica. J. Bacteriol. 183 (2001) 968-979. [PMID: 11208796]
Accepted name: (2,2,3-trimethyl-5-oxocyclopent-3-enyl)acetyl-CoA synthase
Reaction: [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate + ATP + CoA = AMP + diphosphate + [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetyl-CoA
For diagram of reaction click here.
Other name(s): 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-CoA synthetase
Systematic name: [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate:CoA ligase (AMP-forming)
Comments: Isolated from Pseudomonas putida. Forms part of the pathway of camphor catabolism.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Ougham, H.J., Taylor, D.G. and Trudgill, P.W. Camphor revisited: involvement of a unique monooxygenase in metabolism of 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetic acid by Pseudomonas putida. J. Bacteriol. 153 (1983) 140-152. [PMID: 6848481]
Accepted name: [butirosin acyl-carrier protein]—L-glutamate ligase
Reaction: (1) ATP + L-glutamate + BtrI acyl-carrier protein = ADP + phosphate + L-glutamyl-[BtrI acyl-carrier protein]
(2) ATP + L-glutamate + 4-amino butanoyl-[BtrI acyl-carrier protein] = ADP + phosphate + 4-(L-γ-glutamylamino)butanoyl-[BtrI acyl-carrier protein]
Other name(s): [BtrI acyl-carrier protein]—L-glutamate ligase; BtrJ
Systematic name: [BtrI acyl-carrier protein]:L-glutamate ligase (ADP-forming)
Comments: Catalyses two steps in the biosynthesis of the side chain of the aminoglycoside antibiotics of the butirosin family. The enzyme adds one molecule of L-glutamate to a dedicated acyl-carrier protein, and following decarboxylation of the product by EC 4.1.1.95, L-glutamyl-[BtrI acyl-carrier protein] decarboxylase, adds a second L-glutamate molecule. Requires Mg2+ or Mn2+, and activity is enhanced in the presence of Mn2+.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Li, Y., Llewellyn, N.M., Giri, R., Huang, F. and Spencer, J.B. Biosynthesis of the unique amino acid side chain of butirosin: possible protective-group chemistry in an acyl carrier protein-mediated pathway. Chem. Biol. 12 (2005) 665-675. [PMID: 15975512]
Accepted name: 4-hydroxybutyrate—CoA ligase (AMP-forming)
Reaction: ATP + 4-hydroxybutanoate + CoA = AMP + diphosphate + 4-hydroxybutanoyl-CoA
For diagram of reaction click here
Other name(s): 4-hydroxybutyrate-CoA synthetase (ambiguous); 4-hydroxybutyrate:CoA ligase (ambiguous); hbs (gene name); 4-hydroxybutyrate—CoA ligase
Systematic name: 4-hydroxybutanoate:CoA ligase (AMP-forming)
Comments: Isolated from the archaeon Metallosphaera sedula. Involved in the 3-hydroxypropanoate/4-hydroxybutanoate cycle. cf. EC 6.2.1.56, 4-hydroxybutyrate—CoA ligase (ADP-forming).
Links to other databases: BRENDA, EXPASY, ExplorEnz, IUBMB, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Ramos-Vera, W.H., Weiss, M., Strittmatter, E., Kockelkorn, D. and Fuchs, G. Identification of missing genes and enzymes for autotrophic carbon fixation in crenarchaeota. J. Bacteriol. 193 (2011) 1201-1211. [PMID: 21169482]
2. Hawkins, A.S., Han, Y., Bennett, R.K., Adams, M.W. and Kelly, R.M. Role of 4-hydroxybutyrate-CoA synthetase in the CO2 fixation cycle in thermoacidophilic archaea. J. Biol. Chem. 288 (2013) 4012-4022. [PMID: 23258541]
Accepted name: 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate—CoA ligase
Reaction: ATP + 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate + CoA = AMP + diphosphate + 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoyl-CoA
For diagram of reaction click here.
Glossary: 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate = HIP
Other name(s): fadD3 (gene name); HIP—CoA ligase
Systematic name: 3-[(3aS,4S,7aS)-7a-methyl-1,5-dioxo-octahydro-1H-inden-4-yl]propanoate:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from actinobacterium Mycobacterium tuberculosis, catalyses a step in the degradation of cholesterol and cholate. The enzyme is very specific for its substrate, and requires that the side chain at C17 is completely removed.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Horinouchi, M., Hayashi, T., Koshino, H. and Kudo, T. ORF18-disrupted mutant of Comamonas testosteroni TA441 accumulates significant amounts of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid and its derivatives after incubation with steroids. J. Steroid Biochem. Mol. Biol. 101 (2006) 78-84. [PMID: 16891113]
2. Casabon, I., Crowe, A.M., Liu, J. and Eltis, L.D. FadD3 is an acyl-CoA synthetase that initiates catabolism of cholesterol rings C and D in actinobacteria. Mol. Microbiol. 87 (2013) 269-283. [PMID: 23146019]
Accepted name: 3-oxocholest-4-en-26-oate—CoA ligase
Reaction: ATP + (25S)-3-oxocholest-4-en-26-oate + CoA = AMP + diphosphate + (25S)-3-oxocholest-4-en-26-oyl-CoA
For diagram of reaction click here.
Other name(s): fadD19 (gene name)
Systematic name: (25S)-3-oxocholest-4-en-26-oate:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from actinobacterium Mycobacterium tuberculosis, catalyses a step in the degradation of cholesterol. It is responsible for the activation of the C8 side chain. 3β-hydroxycholest-5-en-26-oate can also be used as substrate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Wilbrink, M.H., Petrusma, M., Dijkhuizen, L. and van der Geize, R. FadD19 of Rhodococcus rhodochrous-DSM43269, a steroid-coenzyme A ligase essential for degradation of C-24 branched sterol side chains. Appl. Environ. Microbiol. 77 (2011) 4455-4464. [PMID: 21602385]
2. Casabon, I., Swain, K., Crowe, A.M., Eltis, L.D. and Mohn, W.W. Actinobacterial acyl coenzyme a synthetases involved in steroid side-chain catabolism. J. Bacteriol. 196 (2014) 579-587. [PMID: 24244004]
Accepted name: 2-hydroxy-7-methoxy-5-methyl-1-naphthoate—CoA ligase
Reaction: ATP + 2-hydroxy-7-methoxy-5-methyl-1-naphthoate + CoA = AMP + diphosphate + 2-hydroxy-7-methoxy-5-methyl-1-naphthoyl-CoA
For diagram of reaction click here.
Other name(s): NcsB2
Systematic name: 2-hydroxy-7-methoxy-5-methyl-1-naphthoate:CoA ligase
Comments: The enzyme from the bacterium Streptomyces carzinostaticus is involved in the attachment of the 2-hydroxy-7-methoxy-5-methyl-1-naphthoate moiety of the antibiotic neocarzinostatin. In vitro the enzyme also catalyses the activation of other 1-naphthoic acid analogues, e.g. 2-hydroxy-5-methyl-1-naphthoate or 2,7-dihydroxy-5-methyl-1-naphthoate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Cooke, H.A., Zhang, J., Griffin, M.A., Nonaka, K., Van Lanen, S.G., Shen, B. and Bruner, S.D. Characterization of NcsB2 as a promiscuous naphthoic acid/coenzyme A ligase integral to the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. J. Am. Chem. Soc. 129 (2007) 7728-7729. [PMID: 17539640]
Accepted name: 3-(methylthio)propionyl—CoA ligase
Reaction: ATP + 3-(methylsulfanyl)propanoate + CoA = AMP + diphosphate + 3-(methylsulfanyl)propanoyl-CoA
For diagram of reaction click here.
Other name(s): DmdB; MMPA-CoA ligase; methylmercaptopropionate-coenzyme A ligase; 3-methylmercaptopropionyl-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: E1 ubiquitin-activating enzyme
Reaction: ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Other name(s): ubiquitin activating enzyme; E1; ubiquitin-activating enzyme E1
Systematic name: ubiquitin:[E1 ubiquitin-activating enzyme] ligase (AMP-forming)
Comments: Catalyses the ATP-dependent activation of ubiquitin through the formation of a thioester bond between the C-terminal glycine of ubiquitin and the sulfhydryl side group of a cysteine residue in the E1 protein. The two-step reaction consists of the ATP-dependent formation of an E1-ubiquitin adenylate intermediate in which the C-terminal glycine of ubiquitin is bound to AMP via an acyl-phosphate linkage, then followed by the conversion to an E1-ubiquitin thioester bond via the cysteine residue on E1 in the second step.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Haas, A.L., Warms, J.V., Hershko, A. and Rose, I.A. Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin conjugation. J. Biol. Chem. 257 (1982) 2543-2548. [PMID: 6277905]
2. Huzil, J.T., Pannu, R., Ptak, C., Garen, G. and Ellison, M.J. Direct catalysis of lysine 48-linked polyubiquitin chains by the ubiquitin-activating enzyme. J. Biol. Chem. 282 (2007) 37454-37460. [PMID: 17951259]
3. Zheng, M., Liu, J., Yang, Z., Gu, X., Li, F., Lou, T., Ji, C. and Mao, Y. Expression, purification and characterization of human ubiquitin-activating enzyme, UBE1. Mol. Biol. Rep. 37 (2010) 1413-1419. [PMID: 19343538]
4. Carvalho, A.F., Pinto, M.P., Grou, C.P., Vitorino, R., Domingues, P., Yamao, F., Sa-Miranda, C. and Azevedo, J.E. High-yield expression in Escherichia coli and purification of mouse ubiquitin-activating enzyme E1. Mol Biotechnol 51 (2012) 254-261. [PMID: 22012022]
Accepted name: L-allo-isoleucine:holo-[CmaA peptidyl-carrier protein] ligase
Reaction: ATP + L-allo-isoleucine + holo-[CmaA peptidyl-carrier protein] = AMP + diphosphate + L-allo-isoleucyl-S-[CmaA peptidyl-carrier protein]
Other name(s): CmaA
Systematic name: L-allo-isoleucine:holo-[CmaA peptidyl-carrier protein] ligase (AMP-forming)
Comments: This two-domain protein from the bacterium Pseudomonas syringae contains an adenylation domain (A domain) and a thiolation domain (T domain). It catalyses the adenylation of L-allo-isoleucine and its attachment to the T domain. The enzyme is involved in the biosynthesis of the toxin coronatine, which mimics the plant hormone jasmonic acid isoleucine. Coronatine promotes opening of the plant stomata allowing bacterial invasion, which is followed by bacterial growth in the apoplast, systemic susceptibility, and disease.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Couch, R., O'Connor, S.E., Seidle, H., Walsh, C.T. and Parry, R. Characterization of CmaA, an adenylation-thiolation didomain enzyme involved in the biosynthesis of coronatine. J. Bacteriol. 186 (2004) 35-42. [PMID: 14679222]
Accepted name: medium-chain-fatty-acid—[acyl-carrier-protein] ligase
Reaction: ATP + a medium-chain fatty acid + a holo-[acyl-carrier protein] = AMP + diphosphate + a medium-chain acyl-[acyl-carrier protein]
Other name(s): jamA (gene name)
Systematic name: medium-chain-fatty-acid:[acyl-carrier protein] ligase (AMP-forming)
Comments: The enzyme ligates medium chain fatty acids (with aliphatic chain of 6-12 carbons) to an acyl-carrier protein.
References:
1. Edwards, D.J., Marquez, B.L., Nogle, L.M., McPhail, K., Goeger, D.E., Roberts, M.A. and Gerwick, W.H. Structure and biosynthesis of the jamaicamides, new mixed polyketide-peptide neurotoxins from the marine cyanobacterium Lyngbya majuscula. Chem. Biol. 11 (2004) 817-833. [PMID: 15217615]
2. Zhu, X., Liu, J. and Zhang, W. De novo biosynthesis of terminal alkyne-labeled natural products. Nat. Chem. Biol. 11 (2015) 115-120. [PMID: 25531891]
Accepted name: carnitine–CoA ligase
Reaction: ATP + L-carnitine + CoA = AMP + diphosphate + L-carnitinyl-CoA
Glossary: carnitine = 3-hydroxy-4-(trimethylammonio)butanoate
crotonobetaine = (E)-4-(trimethylammonio)but-2-enoate
γ-butyrobetaine = 4-(trimethylammonio)butanoate
Other name(s): caiC (gene name)
Systematic name: L-carnitine:CoA ligase (AMP-forming)
Comments: The enzyme, originally characterized from the bacterium Escherichia coli, can catalyse the transfer of CoA to L-carnitine, crotonobetaine and γ-butyrobetaine. In vitro the enzyme also exhibits the activity of EC 2.8.3.21, L-carnitine CoA-transferase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Eichler, K., Bourgis, F., Buchet, A., Kleber, H.P. and Mandrand-Berthelot, M.A. Molecular characterization of the cai operon necessary for carnitine metabolism in Escherichia coli. Mol. Microbiol. 13 (1994) 775-786. [PMID: 7815937]
2. Bernal, V., Arense, P., Blatz, V., Mandrand-Berthelot, M.A., Canovas, M. and Iborra, J.L. Role of betaine:CoA ligase (CaiC) in the activation of betaines and the transfer of coenzyme A in Escherichia coli. J. Appl. Microbiol. 105 (2008) 42-50. [PMID: 18266698]
Accepted name: long-chain fatty acid adenylyltransferase FadD28
Reaction: ATP + a long-chain fatty acid + holo-[mycocerosate synthase] = AMP + diphosphate + a long-chain acyl-[mycocerosate synthase] (overall reaction)
(1a) ATP + a long-chain fatty acid = diphosphate + a long-chain acyl-adenylate ester
(1b) a long-chain acyl-adenylate ester + holo-[mycocerosate synthase] = AMP + a long-chain acyl-[mycocerosate synthase]
Other name(s): fadD28 (gene name)
Systematic name: long-chain fatty acid:holo-[mycocerosate synthase] ligase (AMP-forming)
Comments: The enzyme, found in certain mycobacteria, activates long-chain fatty acids by adenylation and transfers them to EC 2.3.1.111, mycocerosate synthase. The enzyme participates in the biosynthesis of the virulent lipids dimycocerosates (DIM) and dimycocerosyl triglycosyl phenolphthiocerol (PGL).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Fitzmaurice, A.M. and Kolattukudy, P.E. Open reading frame 3, which is adjacent to the mycocerosic acid synthase gene, is expressed as an acyl coenzyme A synthase in Mycobacterium bovis BCG. J. Bacteriol. 179 (1997) 2608-2615. [PMID: 9098059]
2. Goyal, A., Yousuf, M., Rajakumara, E., Arora, P., Gokhale, R.S. and Sankaranarayanan, R. Crystallization and preliminary X-ray crystallographic studies of the N-terminal domain of FadD28, a fatty-acyl AMP ligase from Mycobacterium tuberculosis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62 (2006) 350-352. [PMID: 16582482]
3. Arora, P., Goyal, A., Natarajan, V.T., Rajakumara, E., Verma, P., Gupta, R., Yousuf, M., Trivedi, O.A., Mohanty, D., Tyagi, A., Sankaranarayanan, R. and Gokhale, R.S. Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis. Nat. Chem. Biol. 5 (2009) 166-173. [PMID: 19182784]
4. Menendez-Bravo, S., Comba, S., Sabatini, M., Arabolaza, A. and Gramajo, H. Expanding the chemical diversity of natural esters by engineering a polyketide-derived pathway into Escherichia coli. Metab. Eng. 24 (2014) 97-106. [PMID: 24831705]
5. Vergnolle, O., Chavadi, S.S., Edupuganti, U.R., Mohandas, P., Chan, C., Zeng, J., Kopylov, M., Angelo, N.G., Warren, J.D., Soll, C.E. and Quadri, L.E. Biosynthesis of cell envelope-associated phenolic glycolipids in Mycobacterium marinum. J. Bacteriol. 197 (2015) 1040-1050. [PMID: 25561717]
Accepted name: 4-hydroxybenzoate adenylyltransferase FadD22
Reaction: ATP + 4-hydroxybenzoate + holo-[4-hydroxyphenylalkanoate synthase] = AMP + diphosphate + 4-hydroxybenzoyl-[4-hydroxyphenylalkanoate synthase] (overall reaction)
(1a) ATP + 4-hydroxybenzoate = 4-hydroxybenzoyl-adenylate + diphosphate
(1b) 4-hydroxybenzoyl-adenylate + holo-[4-hydroxyphenylalkanoate synthase] = AMP + 4-hydroxybenzoyl-[4-hydroxyphenylalkanoate synthase]
Other name(s): fadD22 (gene name); 4-hydroxybenzoate adenylase
Systematic name: 4-hydroxybenzoate:holo-[4-hydroxyphenylalkanoate synthase] ligase (AMP-forming)
Comments: This mycobacterial enzyme participates in the biosynthesis of phenolphthiocerols. Following the substrate‘s activation by adenylation, it is transferred to an acyl-carrier protein domain within the enzyme, from which it is transferred to EC 2.3.1.261, 4-hydroxyphenylalkanoate synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Simeone, R., Leger, M., Constant, P., Malaga, W., Marrakchi, H., Daffe, M., Guilhot, C. and Chalut, C. Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. FEBS J. 277 (2010) 2715-2725. [PMID: 20553505]
2. Vergnolle, O., Chavadi, S.S., Edupuganti, U.R., Mohandas, P., Chan, C., Zeng, J., Kopylov, M., Angelo, N.G., Warren, J.D., Soll, C.E. and Quadri, L.E. Biosynthesis of cell envelope-associated phenolic glycolipids in Mycobacterium marinum. J. Bacteriol. 197 (2015) 1040-1050. [PMID: 25561717]
Accepted name: 4-hydroxyphenylalkanoate adenylyltransferase FadD29
Reaction: (1) ATP + 17-(4-hydroxyphenyl)heptadecanoate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + diphosphate + 17-(4-hydroxyphenyl)heptadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
(1a) ATP + 17-(4-hydroxyphenyl)heptadecanoate = diphosphate + 17-(4-hydroxyphenyl)heptadecanoyl-adenylate
(1b) 17-(4-hydroxyphenyl)heptadecanoyl-adenylate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + 17-(4-hydroxyphenyl)heptadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
(2) ATP + 19-(4-hydroxyphenyl)nonadecanoate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + diphosphate + 19-(4-hydroxyphenyl)nonadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
(2a) ATP + 19-(4-hydroxyphenyl)nonadecanoate = diphosphate + 19-(4-hydroxyphenyl)nonadecanoyl-adenylate
(2b) 19-(4-hydroxyphenyl)nonadecanoyl-adenylate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + 19-(4-hydroxyphenyl)nonadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
Other name(s): fadD29 (gene name); 4-hydroxyphenylalkanoate adenylase
Systematic name: 4-hydroxyphenylalkanoate:holo-[(phenol)carboxyphthiodiolenone synthase] ligase
Comments: The mycobacterial enzyme participates in the biosynthesis of phenolphthiocerols. Following the substrate’s activation by adenylation, it is transferred to an acyl-carrier protein domain within the enzyme, from which it is transferred to the phenolphthiocerol/phthiocerol polyketide synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Simeone, R., Leger, M., Constant, P., Malaga, W., Marrakchi, H., Daffe, M., Guilhot, C. and Chalut, C. Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. FEBS J. 277 (2010) 2715-2725. [PMID: 20553505]
2. Vergnolle, O., Chavadi, S.S., Edupuganti, U.R., Mohandas, P., Chan, C., Zeng, J., Kopylov, M., Angelo, N.G., Warren, J.D., Soll, C.E. and Quadri, L.E. Biosynthesis of cell envelope-associated phenolic glycolipids in Mycobacterium marinum. J. Bacteriol. 197 (2015) 1040-1050. [PMID: 25561717]
Accepted name: L-firefly luciferin—CoA ligase
Reaction: ATP + L-firefly luciferin + CoA = AMP + diphosphate + L-firefly luciferyl-CoA
Glossary: L-firefly luciferin = (R)-4,5-dihydro-2-(6-hydroxy-1,3-benzothiazol-2-yl)thiazole-4-carboxylate
Other name(s): LUC
Systematic name: (R)-4,5-dihydro-2-(6-hydroxy-1,3-benzothiazol-2-yl)thiazole-4-carboxylate:CoA ligase (AMP-forming)
Comments: This is an alternative activity of the firefly luciferase (EC 1.13.12.7), which the enzyme exhibits under normal conditions only when acting on the L-enantiomer of its substrate. The D-isomer can act as a substrate for the CoA–ligase activity in vitro only under low oxygen conditions that are not found in vivo. The activation of L-firefly luciferin to a CoA ester is a step in a recycling pathway that results in its epimerization to the D enantiomer, which is the only substrate whose oxygenation results in light emission.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Fraga, H., Esteves da Silva, J.C. and Fontes, R. Identification of luciferyl adenylate and luciferyl coenzyme a synthesized by firefly luciferase. Chembiochem 5 (2004) 110-115. [PMID: 14695520]
2. Nakamura, M., Maki, S., Amano, Y., Ohkita, Y., Niwa, K., Hirano, T., Ohmiya, Y. and Niwa, H. Firefly luciferase exhibits bimodal action depending on the luciferin chirality. Biochem. Biophys. Res. Commun. 331 (2005) 471-475. [PMID: 15850783]
3. Viviani, V.R., Scorsato, V., Prado, R.A., Pereira, J.G., Niwa, K., Ohmiya, Y. and Barbosa, J.A. The origin of luciferase activity in Zophobas mealworm AMP/CoA-ligase (protoluciferase): luciferin stereoselectivity as a switch for the oxygenase activity. Photochem Photobiol Sci 9 (2010) 1111-1119. [PMID: 20526507]
4. Maeda, J., Kato, D.I., Okuda, M., Takeo, M., Negoro, S., Arima, K., Ito, Y. and Niwa, K. Biosynthesis-inspired deracemizative production of D-luciferin by combining luciferase and thioesterase. Biochim. Biophys. Acta 1861 (2017) 2112-2118. [PMID: 28454735]
Accepted name: L-proline—[L-prolyl-carrier protein] ligase
Reaction: ATP + L-proline + holo-[L-prolyl-carrier protein] = AMP + diphosphate + L-prolyl-[L-prolyl-carrier protein] (overall reaction)
(1a) ATP + L-proline = diphosphate + (L-prolyl)adenylate
(1b) (L-prolyl)adenylate + holo-[L-prolyl-carrier protein] = AMP + L-prolyl-[L-prolyl-carrier protein]
Other name(s): pltF (gene name); bmp4 (gene name); pigI (gene name)
Systematic name: L-proline:[L-prolyl-carrier protein] ligase (AMP-forming)
Comments: The enzyme participates in the biosynthesis of several pyrrole-containing compounds, such as undecylprodigiosin, prodigiosin, pyoluteorin, and coumermycin A1. It catalyses the activation of L-proline to an adenylate form, followed by its transfer to the 4'-phosphopantheine moiety of an L-prolyl-carrier protein.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Thomas, M.G., Burkart, M.D. and Walsh, C.T. Conversion of L-proline to pyrrolyl-2-carboxyl-S-PCP during undecylprodigiosin and pyoluteorin biosynthesis. Chem. Biol. 9 (2002) 171-184. [PMID: 11880032]
2. Harris, A.K., Williamson, N.R., Slater, H., Cox, A., Abbasi, S., Foulds, I., Simonsen, H.T., Leeper, F.J. and Salmond, G.P. The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation. Microbiology 150 (2004) 3547-3560. [PMID: 15528645]
3. Williamson, N.R., Simonsen, H.T., Ahmed, R.A., Goldet, G., Slater, H., Woodley, L., Leeper, F.J. and Salmond, G.P. Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2-methyl-3-n-amyl-pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces. Mol. Microbiol. 56 (2005) 971-989. [PMID: 15853884]
Accepted name: D-alanine—[D-alanyl-carrier protein] ligase
Reaction: ATP + D-alanine + holo-[D-alanyl-carrier protein] = AMP + diphosphate + D-alanyl-[D-alanyl-carrier protein] (overall reaction)
(1a) ATP + D-alanine = (D-alanyl)adenylate + diphosphate
(1b) (D-alanyl)adenylate + holo-[D-alanyl-carrier protein] = AMP + D-alanyl-[D-alanyl-carrier protein]
Other name(s): dltA (gene name); Dcl
Systematic name: D-alanine:[D-alanyl-carrier protein] ligase
Comments: The enzyme is involved in the modification of wall teichoic acids, as well as type I and IV lipoteichoic acids, with D-alanine residues. It activates D-alanine using ATP to form a high-energy (D-alanyl)adenylate intermediate and subsequently transfers the alanyl moiety to the phosphopantheinyl prosthetic group of a D-alanyl-carrier protein (DltC).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Perego, M., Glaser, P., Minutello, A., Strauch, M.A., Leopold, K. and Fischer, W. Incorporation of D-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis. Identification of genes and regulation. J. Biol. Chem. 270 (1995) 15598-15606. [PMID: 7797557]
2. Yonus, H., Neumann, P., Zimmermann, S., May, J.J., Marahiel, M.A. and Stubbs, M.T. Crystal structure of DltA. Implications for the reaction mechanism of non-ribosomal peptide synthetase adenylation domains. J. Biol. Chem. 283 (2008) 32484-32491. [PMID: 18784082]
3. Du, L., He, Y. and Luo, Y. Crystal structure and enantiomer selection by D-alanyl carrier protein ligase DltA from Bacillus cereus. Biochemistry 47 (2008) 11473-11480. [PMID: 18847223]
4. Osman, K.T., Du, L., He, Y. and Luo, Y. Crystal structure of Bacillus cereus D-alanyl carrier protein ligase (DltA) in complex with ATP. J. Mol. Biol. 388 (2009) 345-355. [PMID: 19324056]
Accepted name: E1 SAMP-activating enzyme
Reaction: ATP + [SAMP]-Gly-Gly + [E1 SAMP-activating enzyme]-L-cysteine = S-[[SAMP]-Gly-Gly]-[[E1 SAMP-activating enzyme]-L-cysteine] + AMP + diphosphate (overall reaction)
(1a) ATP + [SAMP]-Gly-Gly = diphosphate + [SAMP]-Gly-Gly-AMP
(1b) [SAMP]-Gly-Gly-AMP + [E1 SAMP-activating enzyme]-L-cysteine = S-[[SAMP]-Gly-Gly]-[[E1 SAMP-activating enzyme]-L-cysteine] + AMP
Glossary: SAMP = small archaeal modifier protein = ubiquitin-like small archaeal modifier protein
Other name(s): UbaA; SAMP-activating enzyme E1
Systematic name: [SAMP]:[E1 SAMP-activating enzyme] ligase (AMP-forming)
Comments: Contains Zn2+. The enzyme catalyses the activation of SAMPs (Small Archaeal Modifier Proteins), which are ubiquitin-like proteins found only in the Archaea. SAMPs are involved in protein degradation, and also act as sulfur carriers involved in thiolation of tRNA and other metabolites such as molybdopterin. The enzyme catalyses the ATP-dependent formation of a SAMP adenylate intermediate in which the C-terminal glycine of SAMP is bound to AMP via an acyl-phosphate linkage (reaction 1). This intermediate can accept a sulfur atom to form a thiocarboxylate moiety in a mechanism that is not yet understood. Alternatively, the E1 enzyme can transfer SAMP from its activated form to an internal cysteine residue, releasing AMP (reaction 2). In this case SAMP is subsequently transferred to a lysine residue in a target protein in a process termed SAMPylation. Auto-SAMPylation (attachment of SAMP to lysine residues within the E1 enzyme) has been observed. cf. EC 2.7.7.100, SAMP-activating enzyme.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Miranda, H.V., Nembhard, N., Su, D., Hepowit, N., Krause, D.J., Pritz, J.R., Phillips, C., Soll, D. and Maupin-Furlow, J.A. E1- and ubiquitin-like proteins provide a direct link between protein conjugation and sulfur transfer in archaea. Proc. Natl Acad. Sci. USA 108 (2011) 4417-4422. [PMID: 21368171]
2. Maupin-Furlow, J.A. Ubiquitin-like proteins and their roles in archaea. Trends Microbiol 21 (2013) 31-38. [PMID: 23140889]
3. Miranda, H.V., Antelmann, H., Hepowit, N., Chavarria, N.E., Krause, D.J., Pritz, J.R., Basell, K., Becher, D., Humbard, M.A., Brocchieri, L. and Maupin-Furlow, J.A. Archaeal ubiquitin-like SAMP3 is isopeptide-linked to proteins via a UbaA-dependent mechanism. Mol. Cell. Proteomics 13 (2014) 220-239. [PMID: 24097257]
4. Hepowit, N.L., de Vera, I.M., Cao, S., Fu, X., Wu, Y., Uthandi, S., Chavarria, N.E., Englert, M., Su, D., Sll, D., Kojetin, D.J. and Maupin-Furlow, J.A. Mechanistic insight into protein modification and sulfur mobilization activities of noncanonical E1 and associated ubiquitin-like proteins of Archaea. FEBS J. 283 (2016) 3567-3586. [PMID: 27459543]
Accepted name: 4-hydroxybutyrate—CoA ligase (ADP-forming)
Reaction: ATP + 4-hydroxybutanoate + CoA = ADP + phosphate + 4-hydroxybutanoyl-CoA
For diagram of reaction click here
Other name(s): Nmar_0206 (locus name)
Systematic name: 4-hydroxybutanoate:CoA ligase (ADP-forming)
Comments: The enzyme, characterized from the marine ammonia-oxidizing archaeon Nitrosopumilus maritimus, participates in a variant of the 3-hydroxypropanoate/4-hydroxybutanate CO2 fixation cycle. cf. EC 6.2.1.40, 4-hydroxybutyrate—CoA ligase (AMP-forming).
Links to other databases: BRENDA, EXPASY, ExplorEnz, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Konneke, M., Schubert, D.M., Brown, P.C., Hugler, M., Standfest, S., Schwander, T., Schada von Borzyskowski, L., Erb, T.J., Stahl, D.A. and Berg, I.A. Ammonia-oxidizing archaea use the most energy-efficient aerobic pathway for CO2 fixation. Proc. Natl Acad. Sci. USA 111 (2014) 8239-8244. [PMID: 24843170]
Accepted name: long-chain fatty acid adenylase/transferase FadD23
Reaction: (1) ATP + stearate + a holo-[(hydroxy)phthioceranic acid synthase] = AMP + diphosphate + a stearoyl-[(hydroxy)phthioceranic acid synthase] (overall reaction)
(1a) ATP + stearate = diphosphate + (stearoyl)adenylate
(1b) (stearoyl)adenylate + a holo-[(hydroxy)phthioceranic acid synthase] = AMP + a stearoyl-[(hydroxy)phthioceranic acid synthase]
(2) ATP + palmitate + a holo-[(hydroxy)phthioceranic acid synthase] = AMP + diphosphate + a palmitoyl-[(hydroxy)phthioceranic acid synthase] (overall reaction)
(2a) ATP + palmitate = diphosphate + (palmitoyl)adenylate
(2b) (palmitoyl)adenylate + a holo-[(hydroxy)phthioceranic acid synthase] = AMP + a palmitoyl-[(hydroxy)phthioceranic acid synthase]
Other name(s): fadD23 (gene name); long-chain fatty acid adenylyltransferase FadD23
Systematic name: palmitate:holo-[(hydroxy)phthioceranic acid synthase] ligase
Comments: This mycobacterial enzyme activates palmitate and stearate by adenylation, followed by their loading onto the polyketide synthase EC 2.3.1.287, phthioceranic/hydroxyphthioceranic acid synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Gokhale, R.S., Saxena, P., Chopra, T. and Mohanty, D. Versatile polyketide enzymatic machinery for the biosynthesis of complex mycobacterial lipids. Nat. Prod. Rep. 24 (2007) 267-277. [PMID: 17389997]
2. Lynett, J. and Stokes, R.W. Selection of transposon mutants of Mycobacterium tuberculosis with increased macrophage infectivity identifies fadD23 to be involved in sulfolipid production and association with macrophages. Microbiology 153 (2007) 3133-3140. [PMID: 17768256]
Accepted name: isophthalate—CoA ligase
Reaction: ATP + isophthalate + CoA = AMP + diphosphate + isophthalyl-CoA
Other name(s): IPCL
Systematic name: isophthalate:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from the bacterium Syntrophorhabdus aromaticivorans, catalyses the first step in an anaerobic isophthalate degradation pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Junghare, M., Spiteller, D. and Schink, B. Anaerobic degradation of xenobiotic isophthalate by the fermenting bacterium Syntrophorhabdus aromaticivorans. ISME J. 13 (2019) 1252-1268. [PMID: 30647456]
Accepted name: long-chain fatty acid adenylase/transferase FadD26
Reaction: ATP + a long-chain fatty acid + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + diphosphate + a long-chain acyl-[(phenol)carboxyphthiodiolenone synthase] (overall reaction)
(1a) ATP + a long-chain fatty acid = diphosphate + a long-chain fatty-acyl adenylate ester
(1b) a long-chain fatty-acyl adenylate ester + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + a long-chain acyl-[(phenol)carboxyphthiodiolenone synthase]
Glossary: phthiocerols = linear carbohydrates containing one methoxyl group, one methyl group, and two secondary hydroxyl groups that serve as a backbone for certain lipids and glycolipids found in many species of Mycobacteriaceae
arachidate = icosanoate
behenate = docosanoate
lignocerate= tetracosanoate
Other name(s): FadD26
Systematic name: long-chain fatty acid:holo-[(phenol)carboxyphthiodiolenone synthase] ligase (AMP-forming)
Comments: The enzyme, present in pathogenic species of mycobacteria, participates in the pathway for biosynthesis of phthiocerols. It catalyses the adenylation of the long-chain fatty acids arachidate (C20) or behenate (C22) [1] and potentially the very-long-chain fatty acid lignocerate (C24) [2]. The activated fatty acids are then loaded to EC 2.3.1.292, (phenol)carboxyphthiodiolenone synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Azad, A.K., Sirakova, T.D., Fernandes, N.D. and Kolattukudy, P.E. Gene knockout reveals a novel gene cluster for the synthesis of a class of cell wall lipids unique to pathogenic mycobacteria. J. Biol. Chem 272 (1997) 16741-16745. [PMID: 9201977]
2. Simeone, R., Leger, M., Constant, P., Malaga, W., Marrakchi, H., Daffe, M., Guilhot, C. and Chalut, C. Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. FEBS J. 277 (2010) 2715-2725. [PMID: 20553505]
3. Vergnolle, O., Chavadi, S.S., Edupuganti, U.R., Mohandas, P., Chan, C., Zeng, J., Kopylov, M., Angelo, N.G., Warren, J.D., Soll, C.E. and Quadri, L.E. Biosynthesis of cell envelope-associated phenolic glycolipids in Mycobacterium marinum. J. Bacteriol. 197 (2015) 1040-1050. [PMID: 25561717]
Accepted name: marinolic acid—CoA ligase
Reaction: (1) ATP + a marinolic acid + CoA = AMP + diphosphate + a marinoloyl-CoA
(2) ATP + a pseudomonic acid + CoA = AMP + diphosphate + a pseudomonoyl-CoA
Glossary: thiomarinols = natural products that combine monic acid and the compact holothin core of the dithiolopyrrolones.
Other name(s): tmlU (gene name)
Systematic name: marinolic acid:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from the bacterium Pseudoalteromonas sp. SANK 73390, catalyses the CoA acylation of pseudomonic and marinolic acids, as part of the biosynthesis of thiomarinols and related compounds.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Dunn, Z.D., Wever, W.J., Economou, N.J., Bowers, A.A. and Li, B. Enzymatic basis of "hybridity" in thiomarinol biosynthesis. Angew. Chem. Int. Ed. Engl. 54 (2015) 5137-5141. [PMID: 25726835]
Accepted name: salicylate—[aryl-carrier protein] ligase
Reaction: ATP + salicylate + holo-[non-ribosomal peptide synthase] = AMP + diphosphate + salicyl-[non-ribosomal peptide synthase] (overall reaction)
(1a) ATP + salicylate = diphosphate + (salicyl)adenylate
(1b) (salicyl)adenylate + holo-[non-ribosomal peptide synthase] = AMP + salicyl-[non-ribosomal peptide synthase]
Other name(s): pmsE (gene name); pchD (gene name)
Systematic name: salicylate:holo-[non-ribosomal peptide synthase] ligase
Comments: The enzyme catalyses the activation of salicylate to (salicyl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of an aryl-carrier protein, which is often a domain of a larger non-ribosimal peptide synthase. The PmsE enzyme is involved in pseudomonine biosynthesis and transfers the activated salicylate first to itself, and then to a PmsG protein. The PchD enzyme is involved in pyochelin biosynthesis and transfers the activated salicylate directly to the PchE protein.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
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]
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: 3,4-dihydroxybenzoate—[aryl-carrier protein] ligase
Reaction: ATP + 3,4-dihydroxybenzoate + holo-[aryl-carrier protein] = AMP + diphosphate + 3,4-dihydroxybenzoyl-[aryl-carrier protein] (overall reaction)
(1a) ATP + 3,4-dihydroxybenzoate = diphosphate + (3,4-dihydroxybenzoyl)adenylate
(1b) (3,4-dihydroxybenzoyl)adenylate + holo-[aryl-carrier protein] = AMP + 3,4-dihydroxybenzoyl-[aryl-carrier protein]
Other name(s): asbC (gene name)
Systematic name: 3,4-dihydroxybenzoate:[aryl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of 3,4-dihydroxybenzoate to (3,4-dihydroxybenzoyl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of an aryl-carrier protein domain. The aryl-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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Pfleger, B.F., Lee, J.Y., Somu, R.V., Aldrich, C.C., Hanna, P.C. and Sherman, D.H. Characterization and analysis of early enzymes for petrobactin biosynthesis in Bacillus anthracis. Biochemistry 46 (2007) 4147-4157. [PMID: 17346033]
Accepted name: L-arginine—[L-arginyl-carrier protein] ligase
Reaction: ATP + L-arginine + holo-[L-arginyl-carrier protein] = AMP + diphosphate + L-arginyl-[L-arginyl-carrier protein] (overall reaction)
(1a) ATP + L-arginine = diphosphate + (L-arginyl)adenylate
(1b) (L-arginyl)adenylate + holo-[L-arginyl-carrier protein] = AMP + L-arginyl-[L-arginyl-carrier protein]
Other name(s): vabF (gene name)
Systematic name: L-arginine:[L-arginyl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-arginine to (L-arginyl)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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Balado, M., Osorio, C.R. and Lemos, M.L. A gene cluster involved in the biosynthesis of vanchrobactin, a chromosome-encoded siderophore produced by Vibrio anguillarum. Microbiology 152 (2006) 3517-3528. [PMID: 17159203]
Accepted name: E1 NEDD8-activating enzyme
Reaction: ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine = AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
Glossary: NEDD = Neural-precursor-cell Expressed Developmentally Down-regulated protein
Other name(s): NEDD-activating enzyme E1; NAE1 (gene name); UBA3 (gene name)
Systematic name: [NEDD8 protein]:[E1 NEDD8-activating enzyme] ligase (AMP-forming)
Comments: Some RING-type E3 ubiquitin transferase (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form complexes with a cullin scaffold protein and a substrate recognition module, which are known as CRL (Cullin-RING-Ligase) complexes. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. Like ubiquitin, the NEDD8 protein ends with two glycine residues. The E1 NEDD8-activating enzyme activates NEDD8 in an ATP-dependent reaction by forming a high-energy thioester intermediate between NEDD8 and one of its cysteine residues. The activated NEDD8 is subsequently transferred to a cysteine residue of EC 2.3.2.34, E2 NEDD8-conjugating enzyme, and is eventually conjugated to a lysine residue of specific substrates in the presence of the appropriate E3 transferase (EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Osaka, F., Kawasaki, H., Aida, N., Saeki, M., Chiba, T., Kawashima, S., Tanaka, K. and Kato, S. A new NEDD8-ligating system for cullin-4A. Genes Dev. 12 (1998) 2263-2268. [PMID: 9694792]
2. Gong, L. and Yeh, E.T. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J. Biol. Chem. 274 (1999) 12036-12042. [PMID: 10207026]
Accepted name: salicylate—CoA ligase
Reaction: ATP + salicylate + CoA = AMP + diphosphate + salicyl-CoA (overall reaction)
(1a) ATP + salicylate = diphosphate + (salicyl)adenylate
(1b) (salicyl)adenylate + CoA = AMP + salicyl-CoA
Other name(s): sdgA (gene name)
Systematic name: salicylate:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from the bacteria Thauera aromatica and Streptomyces sp. WA46, participates in a salicylate degradation pathway. It activates salicylate by its adenylation to (salicyl)adenylate, followed by the transfer of the activated compound to coenzyme A.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc CAS registry number:
References:
1. Bonting, C.F. and Fuchs, G. Anaerobic metabolism of 2-hydroxybenzoic acid (salicylic acid) by a denitrifying bacterium. Arch. Microbiol. 165 (1996) 402-408. [PMID: 8661934]
2. Ishiyama, D., Vujaklija, D. and Davies, J. Novel pathway of salicylate degradation by Streptomyces sp. strain WA46. Appl. Environ. Microbiol. 70 (2004) 1297-1306. [PMID: 15006746]
Accepted name: glyine—[glycyl-carrier protein] ligase
Reaction: ATP + glycine + holo-[glycyl-carrier protein] = AMP + diphosphate + glycyl-[glycyl-carrier protein] (overall reaction)
(1a) ATP + glycine = diphosphate + (glycyl)adenylate
(1b) (glycyl)adenylate + holo-[glycyl-carrier protein] = AMP + glycyl-[glycyl-carrier protein]
Other name(s): dhbF (gene name); sfmB (gene name)
Systematic name: glycine:[glycyl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of glycine to (glycyl)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. This activity is often found as part of a larger non-ribosomal peptide synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. 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]
2. Li, L., Deng, W., Song, J., Ding, W., Zhao, Q.F., Peng, C., Song, W.W., Tang, G.L. and Liu, W. Characterization of the saframycin A gene cluster from Streptomyces lavendulae NRRL 11002 revealing a nonribosomal peptide synthetase system for assembling the unusual tetrapeptidyl skeleton in an iterative manner. J. Bacteriol. 190 (2008) 251-263. [PMID: 17981978]
Accepted name: L-alanine—[L-alanyl-carrier protein] ligase
Reaction: ATP + L-alanine + holo-[L-alanyl-carrier protein] = AMP + diphosphate + L-alanyl-[L-alanyl-carrier protein] (overall reaction)
(1a) ATP + L-alanine = diphosphate + (L-alanyl)adenylate
(1b) (L-alanyl)adenylate + holo-[L-alanyl-carrier protein] = AMP + L-alanyl-[L-alanyl-carrier protein]
Other name(s): ambB (gene name); phsB (gene name)
Systematic name: L-alanine:[L-alanyl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-alanine to (L-alanyl)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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Schwartz, D., Grammel, N., Heinzelmann, E., Keller, U. and Wohlleben, W. Phosphinothricin tripeptide synthetases in Streptomyces viridochromogenes Tu494. Antimicrob. Agents Chemother. 49 (2005) 4598-4607. [PMID: 16251301]
2. Rojas Murcia, N., Lee, X., Waridel, P., Maspoli, A., Imker, H.J., Chai, T., Walsh, C.T. and Reimmann, C. The Pseudomonas aeruginosa antimetabolite L -2-amino-4-methoxy-trans-3-butenoic acid (AMB) is made from glutamate and two alanine residues via a thiotemplate-linked tripeptide precursor. Front. Microbiol. 6 (2015) 170. [PMID: 25814981]
Accepted name: L-glutamate—[L-glutamyl-carrier protein] ligase
Reaction: ATP + L-glutamate + holo-[L-glutamyl-carrier protein] = AMP + diphosphate + L-glutamyl-[L-glutamyl-carrier protein] (overall reaction)
(1a) ATP + L-glutamate = diphosphate + (L-glutamyl)adenylate
(1b) (L-glutamyl)adenylate + holo-[L-glutamyl-carrier protein] = AMP + L-glutamyl-[L-glutamyl-carrier protein]
Other name(s): ambE (gene name)
Systematic name: L-glutamate:[L-glutamyl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-glutamate to (L-glutamyl)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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Rojas Murcia, N., Lee, X., Waridel, P., Maspoli, A., Imker, H.J., Chai, T., Walsh, C.T. and Reimmann, C. The Pseudomonas aeruginosa antimetabolite L -2-amino-4-methoxy-trans-3-butenoic acid (AMB) is made from glutamate and two alanine residues via a thiotemplate-linked tripeptide precursor. Front. Microbiol. 6 (2015) 170. [PMID: 25814981]
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
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).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
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: indoleacetate—CoA ligase
Reaction: ATP + (indol-3-yl)acetate + CoA = AMP + diphosphate + (indol-3-yl)acetyl-CoA
Other name(s): iaaB (gene name)
Systematic name: (indol-3-yl)acetate:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from the bacterium Aromatoleum aromaticum, is involved in degradation of (indol-3-yl)acetate. It is also active with phenylacetate and the non-physiological compound (2-naphthyl)acetate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Schuhle, K., Nies, J. and Heider, J. An indoleacetate-CoA ligase and a phenylsuccinyl-CoA transferase involved in anaerobic metabolism of auxin. Environ. Microbiol. 18 (2016) 3120-3132. [PMID: 27102732]
Accepted name: malonate—CoA ligase
Reaction: ATP + malonate + CoA = AMP + phosphate + malonyl-CoA
Other name(s): ACSF3 (gene name); AAE13 (gene name); malonyl-CoA synthetase
Systematic name: malonate:CoA ligase (AMP-forming)
Comments: The enzyme, found in mitochondria, detoxifies malonate, which is a potent inhibitor of mitochondrial respiration, and provides malonyl-CoA to the mitochondrial fatty acid biosynthesis pathway.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Gueguen, V., Macherel, D., Jaquinod, M., Douce, R. and Bourguignon, J. Fatty acid and lipoic acid biosynthesis in higher plant mitochondria. J. Biol. Chem. 275 (2000) 5016-5025. [PMID: 10671542]
2. Witkowski, A., Thweatt, J. and Smith, S. Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain extender units for mitochondrial fatty acid synthesis. J. Biol. Chem. 286 (2011) 33729-33736. [PMID: 21846720]
3. Chen, H., Kim, H.U., Weng, H. and Browse, J. Malonyl-CoA synthetase, encoded by Acyl Activating Enzyme13, is essential for growth and development of Arabidopsis. Plant Cell 23 (2011) 2247-2262. [PMID: 21642549]
4. Guan, X. and Nikolau, B.J. AAE13 encodes a dual-localized malonyl-CoA synthetase that is crucial for mitochondrial fatty acid biosynthesis. Plant J. 85 (2016) 581-593. [PMID: 26836315]
5. Bowman, C.E., Rodriguez, S., Selen Alpergin, E.S., Acoba, M.G., Zhao, L., Hartung, T., Claypool, S.M., Watkins, P.A. and Wolfgang, M.J. The mammalian malonyl-CoA synthetase ACSF3 is required for mitochondrial protein malonylation and metabolic efficiency. Cell Chem. Biol. 24 (2017) 673-684.e4. [PMID: 28479296]
6. Bowman, C.E. and Wolfgang, M.J. Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism. Adv Biol Regul 71 (2019) 34-40. [PMID: 30201289]
Accepted name: thioglycine synthase
Reaction: ATP + sulfide + a [methyl-coenzyme M reductase]-glycine = ADP + phosphate + a [methyl-coenzyme M reductase]-thioglycine
Glossary: thioglycine = 2-aminoethanethioic O-acid
Other name(s): ycaO (gene name) (ambiguous)
Systematic name: [methyl-coenzyme M reductase]-glycine—sulfur ligase (thioglycine-forming)
Comments: Requires Mg2+. The enzyme is found in anaerobic methanogenic and methanotrophic archaea, where it modifies a glycine residue in EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase (methyl-CoM reductase). Upon binding to its substrate, an external source of sulfide attacks the target amide bond generating a tetrahedral intermediate. The amide oxyanion attacks the γ-phosphate of ATP, releasing ADP and forming a phosphorylated thiolate intermediate that collapses to form thioglycine and phosphate. In most organisms activity requires a second protein (TfuA) , which may allosterically activate this enzyme or assist in the delivery of sulfide to the substrate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Nayak, D.D., Mahanta, N., Mitchell, D.A. and Metcalf, W.W. Post-translational thioamidation of methyl-coenzyme M reductase, a key enzyme in methanogenic and methanotrophic Archaea. Elife 6 (2017) e29218 . [PMID: 28880150]
2. Mahanta, N., Liu, A., Dong, S., Nair, S.K. and Mitchell, D.A. Enzymatic reconstitution of ribosomal peptide backbone thioamidation. Proc. Natl. Acad. Sci. USA 115 (2018) 3030-3035. [PMID: 29507203]
3. Dong, S.H., Liu, A., Mahanta, N., Mitchell, D.A. and Nair, S.K. Mechanistic basis for ribosomal peptide backbone modifications. ACS Cent. Sci. 5 (2019) 842-851. [PMID: 31139720]
Accepted name: oxazoline synthase
Reaction: (1) ATP + a [protein]-(L-amino acyl-L-serine) = ADP + phosphate + a [protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-2-oxazoline
(2) ATP + a [protein]-(L-amino acyl-L-threonine) = ADP + phosphate + a [protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-5-methyl-2-oxazoline
(3) ATP + a [protein]-(L-amino acyl-L-cysteine) = ADP + phosphate + a [protein]-(1S,4R)-2-(C-substituted-aminomethyl)-4-acyl-2-thiazoline
Other name(s): cyanobactin heterocyclase; cyanobactin cyclodehydratase; patD (gene name); balhD (gene name); micD (gene name)
Systematic name: [peptide]-(L-amino acyl-L-serine) cyclodehydratase (2-oxazoline-forming)
Comments: Requires Mg2+. The enzyme, which participates in the biosynthesis of ribosomal peptide natural products (RiPPs), converts L-cysteine, L-serine and L-threonine residues to thiazoline, oxazoline, and methyloxazoline rings, respectively. The enzyme requires two domains - a cyclodehydratase domain, known as a YcaO domain, and a substrate recognition domain (RRE domain) that controls the regiospecificity of the enzyme. The RRE domain can either be fused to the YcaO domain or occur as a separate protein; however both domains are required for activity. The enzyme can process multiple residues within the same substrate peptide, and all enzymes characterized so far follow a defined order, starting with the L-cysteine closest to the C-terminus. The reaction involves phosphorylation of the preceding ribosomal peptide backbone amide bond, forming ADP and a phosphorylated intermediate, followed by release of the phosphate group. In some cases the enzyme catalyses a side reaction in which the phosphorylated intermediate reacts with ADP to form AMP and diphosphate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc CAS registry number:
References:
1. McIntosh, J.A., Donia, M.S. and Schmidt, E.W. Insights into heterocyclization from two highly similar enzymes. J. Am. Chem. Soc. 132 (2010) 4089-4091. [PMID: 20210311]
2. Melby, J.O., Dunbar, K.L., Trinh, N.Q. and Mitchell, D.A. Selectivity, directionality, and promiscuity in peptide processing from a Bacillus sp. Al Hakam cyclodehydratase. J. Am. Chem. Soc. 134 (2012) 5309-5316. [PMID: 22401305]
3. Ge, Y., Czekster, C.M., Miller, O.K., Botting, C.H., Schwarz-Linek, U. and Naismith, J.H. Insights into the mechanism of the cyanobactin heterocyclase enzyme. Biochemistry 58 (2019) 2125-2132. [PMID: 30912640]
Accepted name: thiazoline synthase
Reaction: ATP + a [protein]-(L-amino acyl-L-cysteine) = ADP + phosphate + a [protein]-(1S,4R)-2-(C-substituted-aminomethyl)-4-acyl-2-thiazoline
Glossary: L-cysteine heterocyclase; truD (gene name); lynD (gene name)
Systematic name: [peptide]-(L-amino acyl-L-cysteine) cyclodehydratase (2-thiazoline-forming)
Comments: Requires Mg2+. The enzyme, which participates in the biosynthesis of some ribosomal peptide natural products (RiPPs) such as the trunkamides, converts L-cysteine residues to thiazoline rings. The enzyme requires two domains - a cyclodehydratase domain, known as a YcaO domain, and a substrate recognition domain (RRE domain) that controls the regiospecificity of the enzyme. The RRE domain can either be fused to the YcaO domain or occur as a separate protein; however both domains are required for activity. The enzyme can process multiple L-cysteine residues within the same substrate peptide, and all enzymes characterized so far follow a defined order, starting with the L-cysteine closest to the C-terminus. The reaction involves phosphorylation of the preceding ribosomal peptide backbone amide bond, forming ADP and a phosphorylated intermediate, followed by release of the phosphate group. In some cases the enzyme catalyses a side reaction in which the phosphorylated intermediate reacts with ADP to form AMP and diphosphate. This activity is also catalysed by the related enzyme EC 6.2.2.2, oxazoline synthase. That enzyme differs by having an RRE domain that also recognizes L-serine and L-threonine residues, which are converted to oxazoline and methyloxazoline rings, respectively.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc CAS registry number:
References:
1. McIntosh, J.A. and Schmidt, E.W. Marine molecular machines: heterocyclization in cyanobactin biosynthesis. ChemBioChem 11 (2010) 1413-1421. [PMID: 20540059]
2. McIntosh, J.A., Donia, M.S. and Schmidt, E.W. Insights into heterocyclization from two highly similar enzymes. J. Am. Chem. Soc. 132 (2010) 4089-4091. [PMID: 20210311]
3. Koehnke, J., Bent, A.F., Zollman, D., Smith, K., Houssen, W.E., Zhu, X., Mann, G., Lebl, T., Scharff, R., Shirran, S., Botting, C.H., Jaspars, M., Schwarz-Linek, U. and Naismith, J.H. The cyanobactin heterocyclase enzyme: a processive adenylase that operates with a defined order of reaction. Angew. Chem. Int. Ed. Engl. 52 (2013) 13991-13996. [PMID: 24214017]
4. Koehnke, J., Mann, G., Bent, A.F., Ludewig, H., Shirran, S., Botting, C., Lebl, T., Houssen, W., Jaspars, M. and Naismith, J.H. Structural analysis of leader peptide binding enables leader-free cyanobactin processing. Nat. Chem. Biol. 11 (2015) 558-563. [PMID: 26098679]
5. Ge, Y., Czekster, C.M., Miller, O.K., Botting, C.H., Schwarz-Linek, U. and Naismith, J.H. Insights into the mechanism of the cyanobactin heterocyclase enzyme. Biochemistry 58 (2019) 2125-2132. [PMID: 30912640]