10.4.4 Cerulenin, a natural inhibitor of fatty acid synthase

Cerulenin is a fungal toxin that binds to and irreversibly inhibits fatty acid synthase. Its structure resembles the β-keto-acyl intermediates (Figure 10.4.4-1), and the active site to which cerulenin binds is the very same one that forms the β-keto-acyl group by condensation. The cysteine in this site then reacts with the epoxide ring in the cerulenin and is alkylated.

While epoxide drugs are not terribly popular because of possible toxicity, there is presently some interest in the development of fatty acid synthase inhibitors, modeled on the structure of cerulenin, for the treatment of obesity.¹

1: I look forward to the discoveries of metabolic derailments these may cause – what is going to become of the surplus acetyl-CoA if fatty acid synthesis is inhibited? Acetic acid? Cholesterol?