Clavulanic acid, a beta-lactamase inhibitor: biosynthesis and molecular genetics.

Abstract:

:Clavulanic acid is a secondary metabolite produced by Streptomyces clavuligerus. It possesses a clavam structure and a characteristic 3R,5R stereochemistry essential for action as a beta-lactamase inhibitory molecule. It is produced from glyceraldehyde-3-phosphate and arginine in an eight step biosynthetic pathway. The pathway is carried out by unusual enzymes, such as (1) the enzyme condensing both precursors, N2-(2-carboxyethyl)-arginine (CEA) synthetase, (2) the beta-lactam synthetase cyclizing CEA and (3) the clavaminate synthetase, a well-characterized multifunctional enzyme. Genes for biosynthesis of clavulanic acid and other clavams have been cloned and characterized. They offer new possibilities for modification of the pathway and for obtaining new molecules with a clavam structure. The state of the regulatory proteins controlling clavulanic acid biosynthesis, as well as the relationship between the biosynthetic pathway of clavulanic acid and other clavams, is discussed.

authors

Liras P,Rodríguez-García A

doi

10.1007/s002530000420

subject

Has Abstract

pub_date

2000-10-01 00:00:00

pages

467-75

issue

4

eissn

0175-7598

issn

1432-0614

journal_volume

54

pub_type

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