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Global rewiring of cellular metabolism renders Saccharomyces cerevisiae Crabtree negative

Author

Listed:
  • Zongjie Dai

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Mingtao Huang

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Yun Chen

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Verena Siewers

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Jens Nielsen

    (Chalmers University of Technology
    Chalmers University of Technology
    Technical University of Denmark
    Beijing University of Chemical Technology)

Abstract

Saccharomyces cerevisiae is a Crabtree-positive eukaryal model organism. It is believed that the Crabtree effect has evolved as a competition mechanism by allowing for rapid growth and production of ethanol at aerobic glucose excess conditions. This inherent property of yeast metabolism and the multiple mechanisms underlying it require a global rewiring of the entire metabolic network to abolish the Crabtree effect. Through rational engineering of pyruvate metabolism combined with adaptive laboratory evolution (ALE), we demonstrate that it is possible to obtain such a global rewiring and hereby turn S. cerevisiae into a Crabtree-negative yeast. Using integrated systems biology analysis, we identify that the global rewiring of cellular metabolism is accomplished through a mutation in the RNA polymerase II mediator complex, which is also observed in cancer cells expressing the Warburg effect.

Suggested Citation

  • Zongjie Dai & Mingtao Huang & Yun Chen & Verena Siewers & Jens Nielsen, 2018. "Global rewiring of cellular metabolism renders Saccharomyces cerevisiae Crabtree negative," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05409-9
    DOI: 10.1038/s41467-018-05409-9
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    Cited by:

    1. Ning Qin & Lingyun Li & Xiaozhen Wan & Xu Ji & Yu Chen & Chaokun Li & Ping Liu & Yijie Zhang & Weijie Yang & Junfeng Jiang & Jianye Xia & Shuobo Shi & Tianwei Tan & Jens Nielsen & Yun Chen & Zihe Liu, 2024. "Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Jianye Xia & Benjamin J. Sánchez & Yu Chen & Kate Campbell & Sergo Kasvandik & Jens Nielsen, 2022. "Proteome allocations change linearly with the specific growth rate of Saccharomyces cerevisiae under glucose limitation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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