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 C-13-labeled precursors to Streptoverticillium fervens HP-891. Although none of the 13 C-labeled acetate was incorporated into FR-900848, the labeling pattern of FR-900848 derived from D-[U-C-13(6)]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-C-13(6)]glucose, [1,3-C-13(2)]glycerol, and L-[Me-C-13]Methionine provided information on the biosynthetic origin of structurally unusual parts (polycyclopropane and aminonucleoside) in this antibiotic. (c) 2006 Elsevier Ltd. All rights reserved.