Cerulenin

Cerulenin is a natural product produced by the fungus Cephalosporium caeruleum. It is used in biochemistry as a potent inhibitor of fatty acid synthesis.

Cerulenin acts by inhibiting the condensing enzyme of fatty acid synthase, specifically the β-ketoacyl-ACP synthase (KAS) enzymes. It binds covalently to an active site cysteine, preventing the condensation reaction that elongates fatty acyl chains. Because KAS domains are shared by type II fatty acid synthases in bacteria and by type I fatty acid synthases in many eukaryotes, cerulenin can block fatty acid synthesis across diverse organisms. It also inhibits certain polyketide synthases that use similar KS domains, making it a useful tool for studying lipid and polyketide biosynthesis.

In research, cerulenin is used to probe the role of fatty acid synthesis in growth and metabolism, to examine the regulation of lipid pathways, and to investigate the function of KS-containing enzymes. It is employed in vitro and in intact cells, typically under controlled laboratory conditions. Its usefulness is balanced by limitations such as toxicity, poor water solubility, and non-specific effects at higher concentrations.

Cerulenin is not clinically approved due to safety and pharmacokinetic concerns. Its primary value remains as a research reagent for dissecting fatty acid and polyketide synthase pathways and for understanding lipid metabolism.