Biosynthetic study of FR-900848: unusual observation on polyketide biosynthesis that did not accept acetate as origin of acetyl-CoA

The biosynthetic pathway of a potent antifungal agent, FR-900848, has been examined by administration of several 13C-labeled precursors to Streptoverticillium fervens HP-891. Although none of the 13C-labeled acetate was incorporated into FR-900848, the labeling pattern of FR-900848 derived from d-[U-13C6]glucose revealed that the fatty acid backbone of FR-900848 has been biosynthesized via a polyketide pathway. These unusual results strongly show that the major pathway to provide acetyl-CoA in this microorganism is glycolysis. Feeding experiments with d-[U-13C6]glucose, [1,3-13C2]glycerol, and l-[Me-13C]methionine provided information on the biosynthetic origin of structurally unusual parts (polycyclopropane and aminonucleoside) in this antibiotic.