Penicillium griseofulvum F1959, high-production strain of pyripyropene a, specific inhibitor of acyl-CoA: cholesterol acyltransferase 2.
نویسندگان
چکیده
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.
منابع مشابه
Phenylpyropene C, a new inhibitor of acyl-CoA: cholesterol acyltransferase produced by Penicillium griseofulvum F1959.
Acyl-CoA: cholesterol acyltransferase (ACAT, EC 2.3.1.26) is responsible for intracellular esterification of cholesterol and plays a key role in intestinal absorption of cholesterol, hepatic production of lipoproteins1,2) and accumulation of cholesteryl esters within macrophages and smooth muscle cells of the atheroma3). Therefore, ACAT is an attractive target for new treatments of hypercholest...
متن کاملPhenylpyropene A and B, new inhibitors of acyl-CoA: cholesterol acyltransferase produced by Penicillium griseofulvum F1959.
Acyl-CoA: cholesterol acyltransferase (ACAT, EC 2.3.1.26) is the primary enzyme responsible for intracellular esterification of cholesterol in intestinal mucosal cells, synthesis of the cholesteryl esters packaged into very-lowdensity lipoproteins (VLDL) secreted by liver, accumulation of cholesteryl esters within macrophages and smooth muscle cells of the atheroma, and plays a key role in form...
متن کاملCharacterization of two acetyltransferase genes in the pyripyropene biosynthetic gene cluster from Penicillium coprobium
Pyripyropenes potently and selectively inhibit acyl-CoA:cholesterol acyltransferase 2 (ACAT-2). Among multiple isomers of pyripyropene (A to R), pyripyropene A (PyA) has insecticidal properties in addition to its growth inhibition properties against human umbilical vein endothelial cells. Based on the predicted biosynthetic gene cluster of pyripyropene A, two genes (ppb8 and ppb9) encoding two ...
متن کاملChemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety.
Structure-activity relationships of the pyridine-pyrone moiety in pyripyropene A (1), a potent acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor of fungal origin, were studied. Several kinds of aromatic or hetero ring substituents for the pyridine moiety were synthesized using unique degradation reaction, following by gamma-acylation. All the six synthesized analogs decreased the inhibitor...
متن کاملACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver.
BACKGROUND Two acyl-coenzyme A:cholesterol acyltransferase (ACAT) genes, ACAT1 and ACAT2, have been identified that encode 2 proteins responsible for intracellular cholesterol esterification. METHODS AND RESULTS In this study, immunohistology was used to establish their cellular localization in human liver biopsies. ACAT2 protein expression was confined to hepatocytes, whereas ACAT1 protein w...
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عنوان ژورنال:
- Journal of microbiology and biotechnology
دوره 18 10 شماره
صفحات -
تاریخ انتشار 2008