Metabolic engineering of a methylmalonyl-CoA mutase--epimerase pathway for complex polyketide biosynthesis in Escherichia coli

The engineered coenzyme B(sub)12-dependent methylmalonyl-CoA mutase--epimerase pathway produces the (2S)-methylmalonyl-CoA extender unit from the succinyl-CoA, instead of prppionyl-CoA as in the propionyl-CoA carboxylase. Isotopic labeling reveals that in the synthesis of polyketide, the starter and extender units are separately derived from exogenous propionate and methylmalonyl-CoA, respectively.