Regulation of lipid biosynthesis in Saccharomyces cerevisiae by fumonisin B sub(1)

The regulation of lipid biosynthesis in the yeast Saccharomyces cerevisiae by fumonisin B sub(1) was examined. Fumonisin B sub(1) inhibited the growth of yeast cells. Cells supplemented with fumonisin B sub(1) accumulated free sphinganine and phytosphingosine in a dose-dependent manner. The cellular concentration of ceramide was reduced in fumonisin B sub(1)-supplemented cells. Ceramide synthase activity was found in yeast cell membranes and was inhibited by fumonisin B sub(1). Fumonisin B sub(1) inhibited the synthesis of the inositol-containing sphingolipids inositol phosphorylceramide, mannosylinositol phosphorylceramide, and mannosyldiinositol phosphorylceramide. Fumonisin B sub(1) also caused a decrease in the synthesis of the major phospholipids synthesized via the CDP-diacylglycerol-dependent pathway and the synthesis of neutral lipids. The effects of fumonisin B sub(1) and sphingoid bases on the activities of enzymes in the pathways leading to the synthesis of sphingolipids, phospholipids, and neutral lipids were also examined. Other than ceramide synthase, fumonisin B sub(1) did not affect the activities of any of the enzymes examined. However, sphinganine and phytosphingosine inhibited the activities of inositol phosphorylceramide synthase, phosphatidylserine synthase, and phosphatidate phosphatase. These are key enzymes responsible for the synthesis of lipids in yeast. The data reported here indicated that the biosynthesis of sphingolipids, phospholipids and neutral lipids was coordinately regulated by fumonisin B sub(1) through the regulation of lipid biosynthetic enzymes by sphingoid bases.