CJ-15,183, a new inhibitor of squalene synthase produced by a fungus, Aspergillus aculeatus

Abstract

A new squalene synthase (SSase) inhibitor, CJ-15,183 (I) was isolated from the fermentation broth of a fungus, Aspergillus aculeatus CL38916. The compound potently inhibited rat liver and Candida albicans microsomal SSases and also inhibited the human enzyme. It also showed antifungal activities against filamentous fungi and a yeast. The structure was determined to be an aliphatic tetracarboxylic acid compound consisting of an alkyl γ-lactone, malic acid and isocitric acid moieties by spectroscopic studies.