Target of inhibition by the anti-lipogenic antibiotic cerulenin of sterol synthesis in yeast

The antibiotic cerulenin inhibited the incorporation of 14C-acetyl-CoA by 67% at a concentration of 9 × 10 −6 M but not that of 14C-HMG-CoA into the non-saponifiable fraction in a cell-free extract of Saccharomyces cerevisiae. Cerulenin markedly inhibited the activity of partially purified HMG-CoA synthase. No inhibition of acetoacetyl-CoA thiolase activity was observed in the same preparation of HMG-CoA synthase. Therefore, cerulenin inhibition of overall sterol synthesis may be accounted for by the specific inhibition of HMG-CoA synthase activity.