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

摘要

The biosynthetic pathway of a potent antifungal agent,FR-900848,has been examined by administration of several ~(13)C-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-~(13)C_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 acet-yl-CoA in this microorganism is glycolysis.Feeding experiments with D-[U-~(13)C_6]glucose,[l,3-~(13)C_2]glycerol,and L-[Me-~(13)C]meth-ionine provided information on the biosynthetic origin of structurally unusual parts (polycyclopropane and aminonucleoside) in this antibiotic.