Lipid engineering reveals regulatory roles for membrane fluidity in yeast flocculation and oxygen-limited growth

Metab Eng. 2017 May:41:46-56. doi: 10.1016/j.ymben.2017.03.002. Epub 2017 Mar 18.


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.

Keywords: Fatty acid unsaturation; Fermentation; Hypoxia; Membrane fluidity; Oxygen-limited growth; Yeast flocculation.

MeSH terms

  • Cell Membrane* / genetics
  • Cell Membrane* / metabolism
  • Flocculation
  • Genetic Engineering*
  • Mannose-Binding Lectins* / biosynthesis
  • Mannose-Binding Lectins* / genetics
  • Membrane Fluidity / genetics*
  • Membrane Lipids* / metabolism
  • Oxygen / metabolism*
  • Saccharomyces cerevisiae Proteins* / biosynthesis
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / growth & development


  • FLO1 protein, S cerevisiae
  • Mannose-Binding Lectins
  • Membrane Lipids
  • Saccharomyces cerevisiae Proteins
  • Oxygen