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

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-
    • Subject Terms:
      Saccharomyces cerevisiae*/genetics ; Saccharomyces cerevisiae*/metabolism ; Pyruvate Dehydrogenase Complex*/metabolism ; Pyruvate Dehydrogenase Complex*/genetics ; Lipid Metabolism*; Saccharomyces cerevisiae Proteins/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Lipids/biosynthesis ; Acetyl Coenzyme A/metabolism ; Gene Expression Regulation, Fungal ; Metabolic Engineering/methods ; Aldehyde Oxidoreductases/metabolism ; Aldehyde Oxidoreductases/genetics
    • 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.
      (© 2024. The Author(s).)
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    • Grant Information:
      11975284 National Natural Science Foundation of China (National Science Foundation of China)
    • Accession Number:
      0 (Pyruvate Dehydrogenase Complex)
      0 (Saccharomyces cerevisiae Proteins)
      0 (Lipids)
      72-89-9 (Acetyl Coenzyme A)
      EC 1.2.1.5 (aldehyde dehydrogenase (NAD(P)+))
      EC 1.2.- (Aldehyde Oxidoreductases)
    • Publication Date:
      Date Created: 20241027 Date Completed: 20241027 Latest Revision: 20241029
    • Publication Date:
      20241029
    • Accession Number:
      PMC11513081
    • Accession Number:
      10.1038/s42003-024-07103-7
    • Accession Number:
      39462103