Using Mortierella alpina as a Novel Platform for Lipid Synthesis Inhibitor Screening

Abstract

The screening method for discovering new lipid synthesis inhibitors has not been well developed. Lipid synthesis genes are responsible for the synthesis of fatty acids in normal and tumor cells. Mortierella alpina(M. alpina) fungus has been found to produce large amounts of fatty acids because it possesses a full complement of lipid synthesis genes. We therefore hypothesized that M. alpina could be a good screening tool to find new compounds that inhibit fatty acid synthesis. We developed a M. alpina liquid culture based method to analyze the inhibitory effects of lipid synthesis inhibitors. We applied a color indicator method to monitor the oil production using some well documented lipid inhibitors (C75, Cerulenin) to verify the system, and analyzing pictures using image analysis software. The experimental drug nocodazole inhibited the lipid production in M. alpina almost to the same extent as the control inhibitors. Compared with biomass and protein levels, there was a profound effect on fatty acid level. We report the development of a fast and effective method for screening lipid synthesis inhibitors which can be used against obesity and cancer. This method can further be used to screen additional lipid and fatty acid synthesis inhibitors from natural compound libraries.