Engineering lipid droplet assembly mechanisms for improved triacylglycerol accumulation in Saccharomyces cerevisiae

Paulo Goncalves Teixeira, Florian David, Verena Siewers, Jens Nielsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Production of triacylglycerols (TAGs) through microbial fermentation is an emerging alternative to plant and animal-derived sources. The yeast Saccharomyces cerevisiae is a preferred organism for industrial use but has natively a very poor capacity of TAG production and storage. Here, we engineered S. cerevisiae for accumulation of high TAG levels through the use of structural and physiological factors that influence assembly and biogenesis of lipid droplets. First, human and fungal perilipin genes were expressed, increasing TAG content by up to 36% when expressing the human perilipin gene PLIN3. Secondly, expression of the FIT2 homologue YFT2 resulted in a 26% increase in TAG content. Lastly, the genes ERD1 and PMR1 were deleted in order to induce an endoplasmic reticulum stress response and stimulate lipid droplet formation, increasing TAG content by 72% for Δ erd1. These new approaches were implemented in previously engineered strains that carry high flux of fatty acid biosynthesis and conversion of acyl-CoA into TAGs, resulting in improvements of up to 138% over those high-producing strains without any substantial growth effects or abnormal cell morphology. We find that these approaches not only represent a significant improvement of S. cerevisiae for TAG production, but also highlight the importance of lipid droplet dynamics for high lipid accumulation in yeast.
Original languageEnglish
Article numberfoy060
JournalFEMS Yeast Research
Volume18
Issue number6
Number of pages11
ISSN1567-1356
DOIs
Publication statusPublished - 2018

Keywords

  • Triacylglycerol
  • Lipid droplet
  • Saccharomyces cerevisiae
  • Perilipin
  • FIT protein
  • ER stress

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