Genetic and biochemical control of phospholipid biosynthesis in Saccharomyces cerevisiae

Abstract

Phospholipid biosynthesis is a highly regulated process in the budding yeast Saccharomyces cerevisiae. This regulation has both genetic and biochemical components. Genetic control is involved in the long-term tailoring of phospholipid biosynthetic levels in response to changing levels of phospholipid precursors in the medium. The CHO1 gene encodes the regulated phospholipid biosynthetic enzyme phosphatidylserine synthase. This enzyme was shown to be regulated at the level of CHO1 gene transcription in response to changing levels of the soluble phospholipid precursors inositol and choline. Regulation of the CHO1 gene was shown to involve both cis- and trans-acting factors that have also been shown to be involved in the regulation of the inositol-1-phosphate synthase gene, INO1, another phospholipid biosynthetic gene. Biochemical control of phospholipid biosynthesis has a number of facets, one of which is competition between the enzymes phosphatidylserine synthase and phosphatidylinositol synthase for their common precursor, CDP-diglyceride. The composition between these enzymes was shown to control the relative flow of material along the arms of the bifurcate glycerophospholipid pathway. This level of control allows the yeast cell to respond rapidly to changes in the levels of the soluble phospholipid precursors inositol and choline in the growth medium. Together the biochemical and genetic regulatory mechanisms described here provide both a gross and a fine tuning of phospholipid biosynthesis in response to changes in the environment of the organism.