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

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 biosy...

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Bibliographic Details
Published in:Applied microbiology and biotechnology 2000-10, Vol.54 (4), p.467-475
Main Authors: LIRAS, P, RODRIGUEZ-GARCIA, A
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - biosynthesis
b-lactamase inhibitors
beta-Lactamase Inhibitors
Biological and medical sciences
Biology of microorganisms of confirmed or potential industrial interest
Biotechnology
clavulanic acid
Clavulanic Acid - biosynthesis
Enzyme Inhibitors - metabolism
Fundamental and applied biological sciences. Psychology
Genes, Bacterial
Genes, Regulator
Mission oriented research
Physiology and metabolism
Streptomyces clavuligerus
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Summary: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.
ISSN:0175-7598
1432-0614
DOI:10.1007/s002530000420