MmfL catalyses formation of a phosphorylated butenolide intermediate in methylenomycin furan biosynthesis

Using a combination of a synthetic substrate analogue and product standard, MmfL, a homologue of the γ-butyrolactone biosynthetic Enzyme AfsA, was shown to catalyse the condensation of dihydroxyacetone phosphate with a β-ketoacyl thioester to form a phosphorylated butenolide intermediate in the biosynthesis of the methylenomycin furans, which induce methlenomycin Antibiotic production in Streptomyces coelicolor A3(2). AfsA homologues are also involved in the biosynthesis of 2-akyl-4-hydroxy-3-methyl butenolide inducers of Antibiotic production in Other Streptomyces species, indicating that diverse signalling molecules are assembled from analogous phosphorylated butenolide intermediates.