BIOSYNTHESIS OF DYNEMICIN-A, A 3-ENE-1,5-DIYNE ANTITUMOR ANTIBIOTIC

Biosynthetic studies of dynemicin A (DNM-A) were carried out by examining the incorporation of singly and doubly C-13-labeled acetates, [methyl-C-13]methionine and [N-15,2-C-13]glycine, into DNM-A by cultures of Micromonospora chersina M956-1. Thc results show that the compound is biosynthesized from two heptaketide chains, which form the bicyclic enediyne core and the anthraquinone moiety, respectively; both are derived from seven head-to-tail coupled acetate units, while the carboxyl group is derived from one carbon of an acetate unit and the O-methyl group from methionine. Intact incorporation of glycine was not observed, but a carbon was incorporated into the O-methyl group. The related C-15 enediyne ring skeletons in the esperamicin/calicheamicin class of antibiotics may be similarly derived as the enediyne core of dynemicin A, but the C-14 cyclic carbonate/bicyclo[7.3.0]dodecadienediyne ring system of neocarzinostatin chromophore A appears to be biosynthesized via a somewhat different process.