STEREOSPECIFIC ACYL TRANSFERS ON THE ERYTHROMYCIN-PRODUCING POLYKETIDE SYNTHASE

During assembly of complex polyketide antibiotics like erythromycin A, molecular recognition by the multienzyme polyketide synthase controls the stereochemical outcome as each successive methylmalonyl-coenzyme A (CoA) extender unit is added. Acylation of the purified erythromycin -producing polyketide synthase has shown that all six acyltransferase domains have identical stereospecificity for their normal substrate (2 S)-methylmalonyl-CoA. In contrast, the configuration of the methyl-bra nched centers in the products, that are derived from (2S)-methylmalony l-CoA, is different. Stereoselection during the chain building process must, therefore, involve additional epimerization steps.