Flow-cytometry-based physiological characterisation and transcriptome analyses reveal a mechanism for reduced cell viability in yeast engineered for increased lipid content

We reported a metabolic engineering strategy for enhanced lipid production in yeast which delivered high per-cell lipid but with low cell growth and compromised physiology

Huadong Peng; Lizhong He; Victoria S. Haritos

2019

Scholarcy highlights

  • Yeast has been the focus of development of cell biofactories for the production of lipids and interest in the field has been driven by the need for sustainably sourced lipids for use in a broad range of industrial applications
  • Regulation of central carbon pathway and lipid production pathway The genes responsible for generating central metabolism precursors for fatty acid biosynthesis such as acetyl-CoA, malonyl-CoA, and acyl-CoA were upregulated in the target strains similar to the pattern of transcriptional rewiring within the central carbon pathway seen in Y. lipolytica engineered for enhanced lipid production via a different approach
  • This study investigated the relationships between transcriptomic profile and cellular physiological responses of yeast engineered for increased lipid production
  • The transcriptomic analysis showed that the lipid engineering strategy redirected the global metabolic pathway towards lipid production, such as upregulated pathways for the production of precursors including acetyl-CoA, malonylCoA, and acyl-CoA
  • These results suggest that current antioxidants treatment and membrane modifications are not efficient enough to mitigate elevated reactive oxygen species levels or benefit membrane integrity and low cell growth
  • The downregulated ATP and NADPH synthesis pathways suggested that the intracellular energy supply was limited and redox levels were unbalanced in the engineered cells where lipid accumulation pathway genes were upregulated
  • The study shows the power of transcriptome and cell physiological analyses to examine cellular performance and direct future engineering efforts

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