REGULATION OF FATTY ACID SYNTHESIS IN YEAST MUTANTS

Abstract

1.In Candida lipolytica, but not in Saccharomyces cerevisiae, cellular fatty acid synthetase levels are severely reduced by a variety of medium and long chain fatty acids. Nevertheless, cellular fatty acid biosynthesis is completely inhibited in both yeasts, under these conditions.2.Saccharomyces cerevisiae mutants deficient in either unsaturated (desaturase mutants) or saturated (acetyl CoA carboxylase or fatty acid synthetase mutants) fatty acid biosynthesis have been isolated. Usually, fatty acid synthetase (fas 1 and fas 2) and acetyl CoA carboxylase (fas 3) mutants grow only when supplemented with a saturated fatty acid of 13–17 carbon atoms chain length. Exceptionally and with limited efficiency, lauric acid or oleic acid may serve as growth supplements, too. To an extent depending on their chain length, the dietary fatty acids are modified by chain elongation chain shortening, desaturation or even saturation. Only with high concentrations of oleic acid, very little modification occurs and, consequently, this acid acid then constitutes over 90% of the cellular fatty acids.3.By the use of acetyl CoA carboxylase mutants, ethidium bromide-induced respiration-deficient fas-mutants and acetyl CoA carboxylase/fatty acid synthetase double mutants it has been shown that in yeast, fatty acyl chain elongation is essentially malonyl-CoA independent and takes place outside the mitochondrial compartment.4.Biochemical and genetic studies on Saccharomyces cerevisiae fatty acid synthetase mutants indicated that the multienzyme complex is basically composed of the two multifunctional polypeptide chains α and β, both encoded by the two unlinked gene loci fas 2 and fas 1, respectively. Component α contains the β-ketoacyl synthetase and the β-ketoacyl reductase active centers as well as the phosphopantetheine binding site. Component β harbors the acetylmalonyl- and palmityl-transferase active sites as well as those of the enoyl reductase and dehydratase. Acetyl- and palmityl-transferase deficiencies are always accompanied by a malonyl-transferase defect, too. Fas 1 and fas 2 are coordinately expressed. The regulatory mechanism involved remains to be elucidated.