Fig 1. Diagrammatic representation of the partial clavulanic acid biosynthetic pathway from Streptomyces clavuligerus.
Genes encoding enzymes known to be involved in the “early” shared stages of 5S clavam and clavulanic acid production, and those predicted to encode proteins involved exclusively in the biosynthesis of clavulanic acid (“late” steps) are indicated. In addition, genes encoding enzymes with known biosynthetic functions are shown next to arrows representing the respective reactions catalyzed by them, and the question mark indicates the unknown protein(s) responsible for the 5S to 5R epimerization and side chain modification of clavam intermediates during clavulanic acid biosynthesis. The two 5S clavam intermediates related to clavaminic acid (R1 = N-glycyl and R2 = N-acetyl-glycyl, respectively), which accumulate in the orf15 and orf16 gene mutants are shown in the dashed box.