title: Membrane engineering of S. cerevisiae targeting sphingolipid metabolism.
abstract: The sustainable production of fuels and chemicals using microbial cell factories is now well established. However, many microbial production processes are still limited in scale due to inhibition from compounds that are present in the feedstock or are produced during fermentation. Some of these inhibitors interfere with cellular membranes and change the physicochemical properties of the membranes. Another group of molecules is dependent on their permeation rate through the membrane for their inhibition. We have investigated the use of membrane engineering to counteract the negative effects of inhibitors on the microorganism with focus on modulating the abundance of complex sphingolipids in the cell membrane of Saccharomyces cerevisiae. Overexpression of ELO3, involved in fatty acid elongation, and AUR1, which catalyses the formation of complex sphingolipids, had no effect on the membrane lipid profile or on cellular physiology. Deletion of the genes ORM1 and ORM2, encoding negative regulators of sphingolipid biosynthesis, decreased cell viability and considerably reduced phosphatidylinositol and complex sphingolipids. Additionally, combining ELO3 and AUR1 overexpression with orm1/2Δ improved cell viability and increased fatty acyl chain length compared with only orm1/2Δ. These findings can be used to further study the sphingolipid metabolism, as well as giving guidance in membrane engineering.
authors.affiliation: Department of Biology and Biological Engineering, Division of Industrial Biotechnology, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Lindahl
authors.affiliation: Department of Biochemistry, University of Geneva, Geneva, Switzerland.|Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Aline X S
authors.initials: AX
authors.lastname: Santos
authors.affiliation: Department of Biology and Biological Engineering, Division of Industrial Biotechnology, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Helén
authors.initials: H
authors.lastname: Olsson
authors.affiliation: Department of Biology and Biological Engineering, Division of Industrial Biotechnology, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Olsson
authors.affiliation: Department of Biology and Biological Engineering, Division of Industrial Biotechnology, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bettiga
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006602:Hexosyltransferases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: C548539:Orm1 protein, S cerevisiae; C548540:Orm2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D000123:Acetyltransferases; C107119:SUR4 protein, S cerevisiae; D006602:Hexosyltransferases; C088714:phosphatidylinositol-ceramide phosphoinositol transferase