Acaterin, a novel inhibitor of acyl-coa: Cholesterol acyltransferase produced by pseudomonas sp. a92

Abstract

Acaterin, a novel inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT), was isolated from a culture broth of Pseudomonas sp. A92 by Diaion HP-20 column chromatography, solvent extraction and reverse phase HPLC. Spectroscopic analyses of the compound yielded 3-(l-hydroxyoctyl)-5-methyl-2(5H)-furanone as the proposed structure. In the presence of oxidized low density lipoprotein, acaterin inhibited the synthesis of cholesteryl ester in macrophage J774 by 50% at a concentration of 45 μM. Acaterin also inhibited ACAT activity in the rat liver microsomes by 50% at a concentration of 120 μM. Kinetic studies suggested that inhibition of ACAT by acaterin was noncompetitive with respect to oleoyl-CoA. © 1992, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.