Clavulanic Acid and Clavams Biosynthesis and Regulation
Paloma Liras, Irene Santamarta and Rosario Pérez-Redondo
from: Streptomyces: Molecular Biology and Biotechnology (Edited by: Paul Dyson). Caister Academic Press, U.K. (2011)
The (3R,5R) clavulanic acid and (3S,5S) clavam molecules share a structure formed by a four member β-lactam and a five member oxaxolidine ring and have several initial common steps in their biosynthesis pathways. The precursors of the molecules are glyceraldehyde-3-phosphate and arginine, condensed by the carboxyethylarginine synthetase (CeaS). The next steps in the pathway occur by the subsequent action of the β-lactam synthase (Bls) forming the β-lactam ring, a proclavaminic acid guanidine hydrolase (PAH) and the clavaminate synthase (Csa2), which forms the two rings clavam structure of clavaminic acid. Modifications of this compound result in late step intermediates for clavulanic acid biosynthesis, N-glycylclavaminic acid or clavaldehyde, and in the clavams structures. In addition to the clavulanic acid gene cluster, two additional clusters containing paralogous genes for clavulanic acid biosynthesis and clavam biosynthesis have been located in S. clavuligerus. Biochemical characterization of the clavam non producer mutants will clarify the biosynthetic pathway of these compounds read more ...