KEGG ORTHOLOGY: K12675

ORTHOLOGY: K12675

Entry

K12675                      KO

Symbol

Name

clavaminate synthase [EC:1.14.11.21]

Pathway

map00331

Clavulanic acid biosynthesis

map01100

Metabolic pathways

map01110

Biosynthesis of secondary metabolites

Module

M00674

Clavaminate biosynthesis, arginine + glyceraldehyde-3P => clavaminate

Reaction

R05466

deoxyamidinoproclavaminate,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

R05468

proclavaminate,2-oxoglutarate:oxygen oxidoreductase (cyclyzing)

R05469

dihydroclavaminate,2-oxoglutarate:oxygen oxidoreductase (desaturating)

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

Other DBs

GO:

0033758

Genes

PCAV:

HPEG:

SFA:

STRP:

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

AG:	AAA26722(cs1)

» show all

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

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]

LinkDB

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 BO, Townsend CA, Solomon EI.

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:

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

LinkDB

REACTION: R05466

Entry

R05466                      Reaction

Name

deoxyamidinoproclavaminate,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Definition

Deoxyguanidinoproclavaminic acid + 2-Oxoglutarate + Oxygen <=> Guanidinoproclavaminic acid + Succinate + CO2

Equation

C06656 + C00026 + C00007 <=> C06657 + C00042 + C00011

Comment

see R05468, R05469

Reaction class

RC00773

C06656_C06657

Enzyme

1.14.11.21

Pathway

rn00331

Clavulanic acid biosynthesis

rn01100

Metabolic pathways

rn01110

Biosynthesis of secondary metabolites

Module

M00674

Clavaminate biosynthesis, arginine + glyceraldehyde-3P => clavaminate

Brite

Enzymatic reactions [BR:br08201]
1. Oxidoreductase reactions
  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
     R05466  Deoxyguanidinoproclavaminic acid + 2-Oxoglutarate + Oxygen <=> Guanidinoproclavaminic acid + Succinate + CO2

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

Other DBs

RHEA:

20024

LinkDB

DBGET integrated database retrieval system