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not yet been fully studied. In our search for new microbial metabolites having inhibitory activity against cholesterol synthesis, phenicin was found to be an active compound. This communication describes studies of the mechanism of action of phenicin. They have demonstrated that it inhibits 3hydroxy-3 -methylglutaryl(H M G)-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis specifically. The enzyme is inactivated irreversibly. Phenicin was obtained by growing Penicillium phoeniceum IFO 5801 as described previously2). The enzymatic synthesis of cholesterol was assayed by measuring the radioactive digitoninprecipitable sterols derived from [14C]acetate, [14C]HMG-CoA or [14C]mevalonate in a rat liver enzyme system as described by Kuroda and Endo6). Phenicin inhibited 50 % sterol synthesis from [14C]acetate at a concentration of 30 ^m. Sterol synthesis from [14C]HMG-CoAwas similarly inhibited by phenicin, while that from [14C]mevalonate was not sensitive to phenicin

Irreversible inhibition of 3-hydroxy-3-methylglutaryl coenzyme a reductase by phenicin (phoenicine).