Abstract
Feeding experiments with isotopically labelled samples of [13C, 2H3-methyl]-thymine, (R, S)-[1-13C]- and (R, S)-[13C-methyl]-β-aminoisobutyrates into monensin-A demonstrate that these metabolites can all contribute to the methylmalonyl-CoA pool in Streptomyces cinnamonensis, and implicate DNA catabolism as a contributory metabolic source of propionate carbon atoms for secondary metabolite biosynthesis. Further, these labelled compounds were unexpectedly incorporated into the butyrate unit of monensin-A, an observation which can be rationalised if β-aminoisobutyrate is converted to methacrylyl-CoA and then reduced to isobutyryl-CoA prior to conversion to butyryl-CoA by the action of isobutyryl-CoA mutase. Feeding experiments with [1-13C]- and [13C-methyl]-methacrylates and [3-13C]-isobutyrate suggest that these metabolites partition similarly between the butyrate and propionate units of monensin-A consistent with the view that isobutyryl-CoA and methacrylyl-CoA have a close metabolic relationship.
