KEGG ENZYME: 1.14.11.21

ENZYME: 1.14.11.21

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

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)

R05466 R05468 R05469

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

ec01110

Biosynthesis of secondary metabolites

Orthology

K12675

clavaminate synthase

Genes

PCAV:

D3880_00620

HPEG:

EAO82_00795

SFA:

Sfla_0558

STRP:

F750_6321

SCLF:

BB341_07820 BB341_13950

SFK:

KY5_8015c

SVR:	CP971_33670

SSPB:

CP982_00555

SOV:	QZH56_31600

SFIY:

F0344_21135

KAB:	B7C62_18900

KAU:	B6264_26740

SVI:	Svir_33410

DHI:	LH044_18215

» show all

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)
DOI:10.1021/bi00222a034

Reference

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

[ag:AAA26722]

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: