Search

Phenylpyropenes A, B, and C, isolated from Penicillium griseofulvum F1959, inhibited DGAT in rat liver microsomes with IC50 values of 78.7+/-1.6, 21.7+/-0.2, and 11.04+/-0.2 mM, respectively. In addition, a kinetic analysis using a Lineweaver-Burk plot revealed that phenylpyropene C was a noncompetitive inhibitor of DGAT. The apparent Michaelis constant (Km) value and inhibition constant (Ki) value were calculated to be 8 mM and 10.4 mM, respectively. Moreover, phenylpyropene C inhibited triglyceride formation in HepG2 cells.

Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification and plays an important role in the intestinal absorption of cholesterol, hepatic production of lipoproteins, and accumulation of cholesteryl ester within cells. During the course of screening to find ACAT inhibitors from microbial sources, the present authors isolated pyripyropene A from Penicillium griseofulvum F1959. Pyripyropene A, an ACAT2-specific inhibitor, has already been produced from Aspergillus fumigatus. Yet, Aspergillus fumigatus is a pathogen and only produces a limited amount of pyripyropene A, making the isolation of pyripyropene A troublesome. In contrast, Penicillium griseofulvum F1959 was found to produce approximately 28 times more pyripyropene A than Aspergillus fumigatus, plus this report also describes the ideal conditions for the production of pyripyropene A by Penicillium griseofulvum F1959 and its subsequent purification.