Expression of two human acyl-CoA:diacylglycerol acyltransferase isozymes in yeast and selectivity of microbial inhibitors toward the isozymes

Junji Inokoshi; Kyosuke Kawamoto; Yoichi Takagi; Maki Matsuhama; Satoshi Omura; Hiroshi Tomoda

doi:10.1038/ja.2008.5

Expression of two human acyl-CoA:diacylglycerol acyltransferase isozymes in yeast and selectivity of microbial inhibitors toward the isozymes

J Antibiot (Tokyo). 2009 Jan;62(1):51-4. doi: 10.1038/ja.2008.5. Epub 2009 Jan 9.

Authors

Junji Inokoshi¹, Kyosuke Kawamoto, Yoichi Takagi, Maki Matsuhama, Satoshi Omura, Hiroshi Tomoda

Affiliation

¹ School of Pharmacy, Kitasato University, Tokyo, Japan.

PMID: 19132064
DOI: 10.1038/ja.2008.5

Abstract

Two isozymes for human acyl-coenzyme A:diacylglycerol acyltransferase (DGAT), DGAT1 and DGAT2, were independently expressed in DGAT-deficient Saccharomyces cerevisiae to establish DGAT1- and DGAT2-S. cerevisiae. The selectivity of DGAT inhibitors of natural origin towards the isozymes was assessed in enzyme assays using the microsomal fractions prepared from DGAT1- and DGAT2-S. cerevisiae. Amidepsines and xanthohumol inhibited DGAT1 and DGAT2 with similar potency, whereas roselipins were found to inhibit DGAT2 selectively.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
DNA, Complementary / genetics
Diacylglycerol O-Acyltransferase / antagonists & inhibitors*
Diacylglycerol O-Acyltransferase / biosynthesis*
Diacylglycerol O-Acyltransferase / genetics
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / biosynthesis
Liver / enzymology
Molecular Sequence Data
Plasmids / genetics
Rats
Reverse Transcriptase Polymerase Chain Reaction
Saccharomyces cerevisiae / enzymology*
Saccharomyces cerevisiae / genetics*

Substances

DNA, Complementary
Enzyme Inhibitors
Isoenzymes
DGAT1 protein, human
DGAT2 protein, human
Diacylglycerol O-Acyltransferase