Biosynthesis of Capreomycin. 2. Incorporation of l-Serine, l-Alanine, and l-2,3-Diaminopropionic Acid

The biosynthesis of the antitubercular antibiotic capreomycin has been studied by administration of isotopically labeled (¹³C and ²H) precursors to Streptomyces capreolus A250. These studies indicated that the 2,3-diaroinopropionate (Dap) moiety of capreomycin is derived from serine via a dehydroalanyl intermediate. The very high incorporation of labeled serine specifically into the serine moiety of capreomycin IA, 1, and incorporation of labeled alanine into the alanine moiety of capreomycin IB, 2, revealed that neither 1 nor 2 is converted into the other. Deuteriated 2,3-diaminopropionic acid was incorporated specifically into the Dap and ^Δ2,3-ureido-Dap residues, demonstrating that it is an intermediate in the biosynthesis of capreomycin and revealing that the pathway involves prepeptide assembly modification of serine.