Communications Biology (Oct 2024)

Regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in Saccharomyces cerevisiae

  • Cairong Lei,
  • Xiaopeng Guo,
  • Miaomiao Zhang,
  • Xiang Zhou,
  • Nan Ding,
  • Junle Ren,
  • Meihan Liu,
  • Chenglin Jia,
  • Yajuan Wang,
  • Jingru Zhao,
  • Ziyi Dong,
  • Dong Lu

DOI
https://doi.org/10.1038/s42003-024-07103-7
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 13

Abstract

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Abstract To achieve high efficiency in microbial cell factories, it is crucial to redesign central carbon fluxes to ensure an adequate supply of precursors for producing high-value compounds. In this study, we employed a multi-omics approach to rearrange the central carbon flux of the pyruvate dehydrogenase (PDH) bypass, thereby enhancing the supply of intermediate precursors, specifically acetyl-CoA. This enhancement aimed to improve the biosynthesis of acetyl-CoA-derived compounds, such as terpenoids and fatty acid-derived molecules, in Saccharomyces cerevisiae. Through transcriptomic and lipidomic analyses, we identified ALD4 as a key regulatory gene influencing lipid metabolism. Genetic validation demonstrated that overexpression of the mitochondrial acetaldehyde dehydrogenase (ALDH) gene ALD4 resulted in a 20.1% increase in lipid production. This study provides theoretical support for optimising the performance of S. cerevisiae as a “cell factory” for the production of commercial compounds.