Cerulenin is an antifungal antibiotic that inhibits fatty acid and steroid biosynthesis. It was the first natural product antibiotic known to inhibit lipid synthesis. In fatty acid synthesis, it has been reported to bind in equimolar ratio to b-keto-acyl-ACP synthase, one of the seven moieties of fatty acid synthase, blocking the interaction of malonyl-CoA. It also has the related activity of stimulating fatty acid oxidation through the activation of CPT1, another enzyme normally inhibited by malonyl-CoA. Inhibition involves covalent thioacylation that permanently inactivates the enzymes. Thes
Cerulenin is an antifungal antibiotic that inhibits fatty acid and steroid biosynthesis. It was the first natural product antibiotic known to inhibit lipid synthesis. In fatty acid synthesis, it has been reported to bind in equimolar ratio to b-keto-acyl-ACP synthase, one of the seven moieties of fatty acid synthase, blocking the interaction of malonyl-CoA. It also has the related activity of stimulating fatty acid oxidation through the activation of CPT1, another enzyme normally inhibited by malonyl-CoA. Inhibition involves covalent thioacylation that permanently inactivates the enzymes. These two behaviors may increase the availability of energy in the form of ATP, perhaps sensed by AMPK, in the hypothalamus.
In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity. It was also reported that cerulenin specifically inhibited fatty acid biosynthesis in Saccharomyces cerevisiae without having an effect on sterol formation. But in general conclusion, cerulenin has inhibitory effects on sterol synthesis.
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