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.