Streptomyces clavuligerus produces the valuable beta-lactamase inhibitor, clavulanic acid, as well as four other structurally related clavam metabolites. These other clavams, collectively referred to as the 5S clavams because their stereochemistry is opposite to the 5R configuration of clavulanic acid, have no commercial value and are of interest largely as unwanted contaminants in clavulanic acid fermentations. However, all clavam metabolites including clavulanic acid share a common biosynthetic pathway, and so attempts to eliminate the 5S clavams must take into account the complex cross regulation between the two arms of the pathway. Genes involved in the production of clavulanic acid and the 5S clavams are also distributed amongst three separate gene clusters. Previous studies have established that ccaR and claR are two regulatory genes that predominantly affect clavulanic acid production. Studies will now be presented to show that an atypical two component regulatory system and a novel hybrid SARP/LuxR type transcriptional regulator specifically regulate 5S clavam production.