Biosynthesis of clavam metabolites.

Naturally occurring clavam metabolites include the valuable β-lactamase inhibitor, clavulanic acid, as well as stereochemical variants with side-chain modifications, called the 5S clavams. Because of the clinical importance of clavulanic acid, most studies of clavam biosynthesis are based on the industrial producer species Streptomyces clavuligerus. Well-characterized early steps in clavam biosynthesis are outlined, and less well understood late steps in 5S clavam biosynthesis are proposed. The complex genetic organization of the clavam biosynthetic genes in S. clavuligerus is described and, where possible, comparisons with other producer species are presented.