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

doi:doi:10.1038/ja.2008.5

The Journal of Antibiotics (2009) 62, 51–54; doi:10.1038/ja.2008.5; published online 9 January 2009

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

Junji Inokoshi¹, Kyosuke Kawamoto¹, Yoichi Takagi¹, Maki Matsuhama¹, Satoshi O macr mura² and Hiroshi Tomoda¹

¹School of Pharmacy, Kitasato University, Tokyo, Japan
²Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan

Correspondence: Dr H Tomoda, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. E-mail: tomodah@pharm.kitasato-u.ac.jp

Received 30 July 2008; Revised 7 October 2008; Accepted 7 October 2008; Published online 9 January 2009.

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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.