KEGG   ORTHOLOGY: K12675Help
Entry
K12675                      KO                                     

Name
cs
Definition
clavaminate synthase [EC:1.14.11.21]
Pathway
ko00331  Clavulanic acid biosynthesis
ko01100  Metabolic pathways
ko01130  Biosynthesis of antibiotics
Module
M00674  Clavaminate biosynthesis, arginine + glyceraldehyde-3P => clavaminate
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09110 Biosynthesis of other secondary metabolites
   00331 Clavulanic acid biosynthesis
    K12675  cs; clavaminate synthase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.14  Acting on paired donors, with incorporation or reduction of molecular oxygen
   1.14.11  With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor
    1.14.11.21  clavaminate synthase
     K12675  cs; clavaminate synthase
BRITE hierarchy
Other DBs
RN: R05466 R05468 R05469
GO: 0033758
Genes
SFA: Sfla_0558
STRP: F750_6321
SCLF: BB341_13950
SFK: KY5_8015c
KAB: B7C62_18900
KAU: B6264_26740
SVI: Svir_33410
AG: AAA26722(cs1)
TaxonomyKoalaUniProt
Reference
PMID:7601835 (Cyanobacteria_CYB)
  Authors
Wu TK, Busby RW, Houston TA, McIlwaine DB, Egan LA, Townsend CA
  Title
Identification, cloning, sequencing, and overexpression of the gene encoding proclavaminate amidino hydrolase and characterization of protein function in clavulanic acid biosynthesis.
  Journal
J Bacteriol 177:3714-20 (1995)
DOI:10.1128/JB.177.13.3714-3720.1995
Reference
  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

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
ec01100  Metabolic pathways
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

KEGG   REACTION: R05469Help
Entry
R05469                      Reaction                               

Name
dihydroclavaminate,2-oxoglutarate:oxygen oxidoreductase (desaturating)
Definition
Dihydroclavaminic acid + Oxygen + 2-Oxoglutarate <=> Clavaminic acid + Succinate + CO2 + H2O
Equation
Comment
Reaction class
RC01391  C06659_C06660
Enzyme
Pathway
rn00331  Clavulanic acid biosynthesis
rn01100  Metabolic pathways
rn01130  Biosynthesis of antibiotics
Module
M00674  Clavaminate biosynthesis, arginine + glyceraldehyde-3P => clavaminate
Orthology
K12675  clavaminate synthase [EC:1.14.11.21]
Reference
1  [PMID:9614345]
  Authors
McGowan SJ, Bycroft BW, Salmond GP.
  Title
Bacterial production of carbapenems and clavams: evolution of beta-lactam antibiotic pathways.
  Journal
Trends Microbiol 6:203-8 (1998)
DOI:10.1016/S0966-842X(98)01251-7

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