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Rewiring carbon metabolism in yeast for high level production of aromatic chemicals

Author

Listed:
  • Quanli Liu

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Tao Yu

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Xiaowei Li

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Yu Chen

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Kate Campbell

    (Chalmers University of Technology
    Chalmers University of Technology)

  • Jens Nielsen

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

  • Yun Chen

    (Chalmers University of Technology
    Chalmers University of Technology)

Abstract

The production of bioactive plant compounds using microbial hosts is considered a safe, cost-competitive and scalable approach to their production. However, microbial production of some compounds like aromatic amino acid (AAA)-derived chemicals, remains an outstanding metabolic engineering challenge. Here we present the construction of a Saccharomyces cerevisiae platform strain able to produce high levels of p-coumaric acid, an AAA-derived precursor for many commercially valuable chemicals. This is achieved through engineering the AAA biosynthesis pathway, introducing a phosphoketalose-based pathway to divert glycolytic flux towards erythrose 4-phosphate formation, and optimizing carbon distribution between glycolysis and the AAA biosynthesis pathway by replacing the promoters of several important genes at key nodes between these two pathways. This results in a maximum p-coumaric acid titer of 12.5 g L−1 and a maximum yield on glucose of 154.9 mg g−1.

Suggested Citation

  • Quanli Liu & Tao Yu & Xiaowei Li & Yu Chen & Kate Campbell & Jens Nielsen & Yun Chen, 2019. "Rewiring carbon metabolism in yeast for high level production of aromatic chemicals," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12961-5
    DOI: 10.1038/s41467-019-12961-5
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    Cited by:

    1. Liu, Ruo-Ying & Lan, Hai-Na & Liu, Zhi-Hua & Li, Bing-Zhi & Yuan, Ying-Jin, 2024. "Microbial valorization of lignin toward coumarins: Challenges and perspectives," Renewable and Sustainable Energy Reviews, Elsevier, vol. 191(C).
    2. 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.
    3. Quanli Liu & Yi Liu & Gang Li & Otto Savolainen & Yun Chen & Jens Nielsen, 2021. "De novo biosynthesis of bioactive isoflavonoids by engineered yeast cell factories," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    4. Meirong Gao & Yuxin Zhao & Zhanyi Yao & Qianhe Su & Payton Van Beek & Zengyi Shao, 2023. "Xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Hongjiao Zhang & Zixin Li & Shuang Zhou & Shu-Ming Li & Huomiao Ran & Zili Song & Tao Yu & Wen-Bing Yin, 2022. "A fungal NRPS-PKS enzyme catalyses the formation of the flavonoid naringenin," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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