A yeast-based tool for mammalian DGATs inhibitors screening

Abstract

AbstractDysregulation of lipid metabolism is associated with obesity, metabolic diseases but there is also increasing evidences of a relationship between lipid bodies (LBs) excess and some cancer. LBs synthesis requires diacylglycerol acyltransferases (DGATs) which catalyses the last step of triacylglycerol (TAG) synthesis, the main storage lipid form in lipid bodies. DGATs and in particular DGAT2, are therefore considered as potential therapeutic targets for the control of these pathologies. Here, the murine and the human DGAT2 were overexpressed in the oleaginous yeast Yarrowia lipolytica deleted for all DGATs activities, for evaluating the functionality of the enzymes in this heterologous host and to evaluate DGAT activity inhibitors. This work provide evidence that mammalian DGATs expressed in Y. lipolytica is a useful tool for screening chemical libraries to identify potential inhibitors or activators of these enzymes of therapeutic interest.