The Enzyme Database

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Accepted name: clavaminate synthase
Reaction: (1) deoxyamidinoproclavaminate + 2-oxoglutarate + O2 = amidinoproclavaminate + succinate + CO2
(2) proclavaminate + 2-oxoglutarate + O2 = dihydroclavaminate + succinate + CO2 + H2O
(3) dihydroclavaminate + 2-oxoglutarate + O2 = clavaminate + succinate + CO2 + H2O
For diagram of clavulanate biosynthesis, click here
Other name(s): clavaminate synthase 2; clavaminic acid synthase
Systematic name: deoxyamidinoproclavaminate,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)
Comments: Contains nonheme iron. Catalyses three separate oxidative reactions in the pathway for the biosythesis of the β-lactamase inhibitor clavulanate in Streptomyces clavuligerus. The first step (hydroxylation) is separated from the latter two (oxidative cyclization and desaturation) by the action of EC, proclavaminate amidinohydrolase. The three reactions are all catalysed at the same nonheme iron site.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 122799-56-8
1.  Salowe, S.P., Krol, W.J., Iwatareuyl, D. and Townsend, C.A. Elucidation of the order of oxidations and identification of an intermediate in the multistep clavaminate synthase reaction. Biochemistry 30 (1991) 2281–2292. [PMID: 1998687]
2.  Zhou, J., Gunsior, M., Bachmann, B.O., Townsend, C.A. and Solomon, E.I. Substrate binding to the α-ketoglutarate-dependent non-heme iron enzyme clavaminate synthase 2: Coupling mechanism of oxidative decarboxylation and hydroxylation. J. Am. Chem. Soc. 120 (1998) 13539–13540.
3.  Zhang, Z.H., Ren, J.S., Stammers, D.K., Baldwin, J.E., Harlos, K. and Schofield, C.J. Structural origins of the selectivity of the trifunctional oxygenase clavaminic acid synthase. Nat. Struct. Biol. 7 (2000) 127–133. [PMID: 10655615]
4.  Zhou, J., Kelly, W.L., Bachmann, B.O., Gunsior, M., Townsend, C.A. and Solomon, E.I. Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional α-KG-dependent non-heme iron enzyme: Correlation with mechanisms and reactivities. J. Am. Chem. Soc. 123 (2001) 7388–7398. [PMID: 11472170]
5.  Townsend, C.A. New reactions in clavulanic acid biosynthesis. Curr. Opin. Chem. Biol. 6 (2002) 583–589. [PMID: 12413541]
[EC created 2003]

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