KEGG   ENZYME: 1.14.11.21Help
Entry
EC 1.14.11.21               Enzyme                                 

Name
clavaminate synthase;
clavaminate synthase 2;
clavaminic acid synthase
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor
BRITE hierarchy
Sysname
deoxyamidinoproclavaminate,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)
Reaction(IUBMB)
(1) deoxyamidinoproclavaminate + 2-oxoglutarate + O2 = amidinoproclavaminate + succinate + CO2 [RN:R05466];
(2) proclavaminate + 2-oxoglutarate + O2 = dihydroclavaminate + succinate + CO2 + H2O [RN:R05468];
(3) dihydroclavaminate + 2-oxoglutarate + O2 = clavaminate + succinate + CO2 + H2O [RN:R05469]
Reaction(KEGG)
Substrate
deoxyamidinoproclavaminate [CPD:C06656];
2-oxoglutarate [CPD:C00026];
O2 [CPD:C00007];
proclavaminate [CPD:C06658];
dihydroclavaminate [CPD:C06659]
Product
amidinoproclavaminate [CPD:C06657];
succinate [CPD:C00042];
CO2 [CPD:C00011];
dihydroclavaminate [CPD:C06659];
H2O [CPD:C00001];
clavaminate [CPD:C06660]
Comment
Contains nonheme iron. Catalyses three separate oxidative reactions in the pathway for the biosythesis of the beta-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 3.5.3.22, proclavaminate amidinohydrolase. The three reactions are all catalysed at the same nonheme iron site.
History
EC 1.14.11.21 created 2003
Pathway
ec00331  Clavulanic acid biosynthesis
ec01130  Biosynthesis of antibiotics
Orthology
K12675  clavaminate synthase
Genes
SFA: Sfla_0558
STRP: F750_6321
SCLF: BB341_13950
SFK: KY5_8015c
KAB: B7C62_18900
KAU: B6264_26740
SVI: Svir_33410
Taxonomy
Reference
1  [PMID:1998687]
  Authors
Salowe SP, Krol WJ, Iwata-Reuyl D, Townsend CA.
  Title
Elucidation of the order of oxidations and identification of an intermediate in the multistep clavaminate synthase reaction.
  Journal
Biochemistry 30:2281-92 (1991)
Reference
2
  Authors
Zhou, J., Gunsior, M., Bachmann, B.O., Townsend, C.A. and Solomon, E.I.
  Title
Substrate binding to the alpha-ketoglutarate-dependent non-heme iron enzyme clavaminate synthase 2: Coupling mechanism of oxidative decarboxylation and hydroxylation.
  Journal
J Am Chem Soc 120:13539-13540 (1998)
Reference
3  [PMID:10655615]
  Authors
Zhang Z, Ren J, Stammers DK, Baldwin JE, Harlos K, Schofield CJ.
  Title
Structural origins of the selectivity of the trifunctional oxygenase clavaminic acid synthase.
  Journal
Nat Struct Biol 7:127-33 (2000)
DOI:10.1038/72398
  Sequence
Reference
4  [PMID:11472170]
  Authors
Zhou J, Kelly WL, Bachmann BO, Gunsior M, Townsend CA, Solomon EI.
  Title
Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional alpha-KG-dependent non-heme iron enzyme: correlation with mechanisms and reactivities.
  Journal
J Am Chem Soc 123:7388-98 (2001)
DOI:10.1021/ja004025+
Reference
5  [PMID:12413541]
  Authors
Townsend CA.
  Title
New reactions in clavulanic acid biosynthesis.
  Journal
Curr Opin Chem Biol 6:583-9 (2002)
DOI:10.1016/S1367-5931(02)00392-7
Other DBs
ExplorEnz - The Enzyme Database: 1.14.11.21
IUBMB Enzyme Nomenclature: 1.14.11.21
ExPASy - ENZYME nomenclature database: 1.14.11.21
BRENDA, the Enzyme Database: 1.14.11.21
CAS: 122799-56-8

DBGET integrated database retrieval system