Biosynthesis of the polyether antibiotic monensin-A. Results from the incorporations of labelled acetate and propionate as a probe of the carbon chain assembly processes

Abstract

The incorporation of sodium [2-²H₂]- and (S)-[2-²H₁]-propionate into the polyether antibiotic monensin-A in cultures of Streptomyces cinnamonensis occurs with retention of label only at C-4 and C-6, whereas during the incorporation of sodium (R)-[2-²H₁]propionate the deuterium label is lost to the medium. These results are consistent with the formation of (S)-methylmalonyl-CoA from the labelled propionate by carboxylation of propionyl-CoA with loss of the 2-pro-R hydrogen. The (S)-methylmalonyl-CoA is subsequently incorporated into the antibiotic by a decarboxylative condensation occurring with overall inversion. The incorporations of sodium [1-¹³C,2-²-H₃]-and [2-¹³C,2-²H₃]-acetates into monensin-A provide evidence for a pathway of metabolism leading to methylmalonyl-CoA that does not proceed via succinyl-CoA. Instead, acetyl-CoA may be processed via butyryl-CoA and isobutyryl-CoA, to afford (S)-methylmalonyl-CoA.