Saccharomyces cerevisiae Δ9‐desaturase Ole1 Interacts with Lipid Biosynthetic Enzymes that Produce Storage Lipid, Phospholipid, and Sterol‐esters

Abstract

Lipids are essential both for integrity of membranes and energy storage in a variety of organisms, from yeast to humans. The chemical properties of membrane phospholipids and triacylglycerol are determined by the composition and organization of their acyl chain components. Acyl-CoA molecules are delivered to the enzymes involved in lipid biosynthesis in a specific order, as is evidenced by the high prevalence of unsaturated acyl chains in the second position of phosphatidic acid and triacylglycerol in Saccharomyces cerevisiae. The mechanism controlling the specific nature of these lipids is not yet known, but we have previously demonstrated that acyltransferases that produce both storage and membrane lipid interact with the Δ9-desaturase, Ole1, in a complex we have called the desaturasome. We propose that these interactions determine the incorporation of unsaturated acyl chains into phospholipid and triacylglycerol and thus control the composition of membrane and storage lipids. Yeast two-hybrid and coimmunoprecipitation studies have revealed novel protein-protein interactions between Ole1 and storage lipid, phospholipid, and sterol-ester biosynthesis enzymes. Notably, Ole1 has been found to interact with the acyl-CoA:sterol acyltransferases Are1 and Are2, phosphatidate cytidylyltransferase Cds1, phosphatidylserine synthase Cho1, phosphatidylinositol synthase Pis1, phosphatidylethanolamine methyltransferase Cho2, and the rate limiting step in sterol synthesis, HMG-CoA reductase Hmg1. This research has determined the composition of an interactome that may exist to regulate the order of acyl chain incorporation into phospholipid, triacylglycerol, and sterol-esters. Future research aims to determine exactly how these interactions control lipid synthesis and composition via metabolic flux analysis and gene deletion studies. Investigating this lipid biosynthesis complex will have implications for a wide variety of applied research, from treating lipid dysregulation in humans to biofuel production by microbes.