Lipid engineering reveals regulatory roles for membrane fluidity in yeast flocculation and oxygen-limited growth.
Cells modulate lipid metabolism in order to maintain membrane homeostasis. Here we use a metabolic engineering approach to manipulate the stoichiometry of fatty acid unsaturation, a regulator of cell membrane fluidity, in Saccharomyces cerevisiae. Unexpectedly, reduced lipid unsaturation triggered cell-cell adhesion (flocculation), a phenomenon characteristic of industrial yeast but uncommon in laboratory strains. We find that ER lipid saturation sensors induce expression of FLO1 - encoding a cell wall polysaccharide binding protein - independently of its canonical regulator. In wild-type cells, Flo1p-dependent flocculation occurs under oxygen-limited growth, which reduces unsaturated lipid synthesis and thus serves as the environmental trigger for flocculation. Transcriptional analysis shows that FLO1 is one of the most highly induced genes in response to changes in lipid unsaturation, and that the set of membrane fluidity-sensitive genes is globally activated as part of the cell's long-term response to hypoxia during fermentation. Our results show how the lipid homeostasis machinery of budding yeast is adapted to carry out a broad response to an environmental stimulus important in biotechnology.
Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany.
Daniel
D
Degreif
Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
Tristan
T
de Rond
Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany.
Adam
A
Bertl
Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemical & Biomolecular Engineering, University of California, Berkeley, Berkeley CA 94720, USA; Department of Bioengineering, University of California, Berkeley, Berkeley CA 94720, USA; QB3 Institute, University of California, Berkeley, Berkeley, CA 94270, USA; Biological Systems & Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; The Novo Nordisk Foundation Center for Sustainability, Technical University of Denmark, Denmark.
Jay D
JD
Keasling
Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Department of Chemical & Biomolecular Engineering, University of California, Berkeley, Berkeley CA 94720, USA; QB3 Institute, University of California, Berkeley, Berkeley, CA 94270, USA. Electronic address: budin@berkeley.edu.
Itay
I
Budin
D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D005427:Flocculation; D005818:Genetic Engineering; D037241:Mannose-Binding Lectins / Q000096:biosynthesis / Q000235:genetics; D008560:Membrane Fluidity / Q000235:genetics*; D008563:Membrane Lipids / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics
C087578:FLO1 protein, S cerevisiae; D037241:Mannose-Binding Lectins; D008563:Membrane Lipids; D029701:Saccharomyces cerevisiae Proteins; D010100:Oxygen
Fatty acid unsaturation; Fermentation; Hypoxia; Membrane fluidity; Oxygen-limited growth; Yeast flocculation