Oligomycin biosynthesis

Oligomycin [63] (Fig. 13) is a 26-membered macrocyclic lactone produced by avermectin-producing Streptomyces avermitilis. The formation of oligomycin backbone requires 16 cycles of condensations. A region encoding polyketide synthase of oligomycin biosynthesis was cloned by transposon-induced mutagenesis. 

The discovery of the entire gene cluster for oligomycin biosynthesis was accomplished by means of chromosomal walking. Seven polyketide synthases are involved in the formation of oligomycin backbone. 

A pathway for fatty acid activation, involving a reaction with nonphosphorylated high-energy intermediates rather than the formation of acetyl-CoA derivatives has also been postulated. The supporting evidence includes the observations that (1) blocking the electron transport chain with cyanide or uncoupling oxidative phosphorylation with dinitrophenol interferes with the fatty acid oxidation (2) oligomycin, which blocks the biosynthesis of ATP but does not affect the formation... 

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