GYPSETIN, A NEW INHIBITOR OF ACYL-COA - CHOLESTEROL ACYLTRANSFERASE PRODUCED BY NANNIZZIA-GYPSEA VAR INCURVATA IFO-9228 .1. FERMENTATION, ISOLATION, PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL-ACTIVITY

A novel inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), desi gnated gypsetin, was isolated from the cultured broth of Nannizzia gyp sea var. incurvata IFO 9228 by solvent extraction, silica gel chromato graphy and crystallization. Gypsetin inhibited rat liver microsomal AC AT activity competitively with respect to the substrate oleoyl-CoA wit h an apparent Ki value of 5.5 mu M. In cultured macrophage J774 cells incubated with oxidized low density lipoprotein, gypsetin inhibited ch olesteryl ester formation from [C-14]oleate by 50% at a concentration of 0.65 mu M without affecting cell surface binding, uptake and degrad ation of the lipoprotein.