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Protein engineering and iterative multimodule optimization for vitamin B6 production in Escherichia coli

Author

Listed:
  • Linxia Liu

    (Chinese Academy of Sciences
    National Technology Innovation Center of Synthetic Biology
    Chinese Academy of Sciences)

  • Jinlong Li

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yuanming Gai

    (Chinese Academy of Sciences
    National Technology Innovation Center of Synthetic Biology)

  • Zhizhong Tian

    (Chinese Academy of Sciences)

  • Yanyan Wang

    (Chinese Academy of Sciences)

  • Tenghe Wang

    (Chinese Academy of Sciences)

  • Pi Liu

    (Chinese Academy of Sciences)

  • Qianqian Yuan

    (Chinese Academy of Sciences)

  • Hongwu Ma

    (Chinese Academy of Sciences)

  • Sang Yup Lee

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Dawei Zhang

    (Chinese Academy of Sciences
    National Technology Innovation Center of Synthetic Biology
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Vitamin B6 is an essential nutrient with extensive applications in the medicine, food, animal feed, and cosmetics industries. Pyridoxine (PN), the most common commercial form of vitamin B6, is currently chemically synthesized using expensive and toxic chemicals. However, the low catalytic efficiencies of natural enzymes and the tight regulation of the metabolic pathway have hindered PN production by the microbial fermentation process. Here, we report an engineered Escherichia coli strain for PN production. Parallel pathway engineering is performed to decouple PN production and cell growth. Further, protein engineering is rationally designed including the inefficient enzymes PdxA, PdxJ, and the initial enzymes Epd and Dxs. By the iterative multimodule optimization strategy, the final strain produces 1.4 g/L of PN with productivity of 29.16 mg/L/h by fed-batch fermentation. The strategies reported here will be useful for developing microbial strains for the production of vitamins and other bioproducts having inherently low metabolic fluxes.

Suggested Citation

  • Linxia Liu & Jinlong Li & Yuanming Gai & Zhizhong Tian & Yanyan Wang & Tenghe Wang & Pi Liu & Qianqian Yuan & Hongwu Ma & Sang Yup Lee & Dawei Zhang, 2023. "Protein engineering and iterative multimodule optimization for vitamin B6 production in Escherichia coli," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40928-0
    DOI: 10.1038/s41467-023-40928-0
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    References listed on IDEAS

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    1. Huan Fang & Dong Li & Jie Kang & Pingtao Jiang & Jibin Sun & Dawei Zhang, 2018. "Metabolic engineering of Escherichia coli for de novo biosynthesis of vitamin B12," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Peter Rugbjerg & Nils Myling-Petersen & Andreas Porse & Kira Sarup-Lytzen & Morten O. A. Sommer, 2018. "Diverse genetic error modes constrain large-scale bio-based production," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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    Cited by:

    1. Daniel P. Cetnar & Ayaan Hossain & Grace E. Vezeau & Howard M. Salis, 2024. "Predicting synthetic mRNA stability using massively parallel kinetic measurements, biophysical modeling, and machine learning," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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