IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40928-0.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40928-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-40928-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. François Bertaux & Sebastián Sosa-Carrillo & Viktoriia Gross & Achille Fraisse & Chetan Aditya & Mariela Furstenheim & Gregory Batt, 2022. "Enhancing bioreactor arrays for automated measurements and reactive control with ReacSight," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Alex J. H. Fedorec & Neythen J. Treloar & Ke Yan Wen & Linda Dekker & Qing Hsuan Ong & Gabija Jurkeviciute & Enbo Lyu & Jack W. Rutter & Kathleen J. Y. Zhang & Luca Rosa & Alexey Zaikin & Chris P. Bar, 2024. "Emergent digital bio-computation through spatial diffusion and engineered bacteria," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Qian Kang & Huan Fang & Mengjie Xiang & Kaixing Xiao & Pingtao Jiang & Chun You & Sang Yup Lee & Dawei Zhang, 2023. "A synthetic cell-free 36-enzyme reaction system for vitamin B12 production," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Noor Radde & Genevieve A. Mortensen & Diya Bhat & Shireen Shah & Joseph J. Clements & Sean P. Leonard & Matthew J. McGuffie & Dennis M. Mishler & Jeffrey E. Barrick, 2024. "Measuring the burden of hundreds of BioBricks defines an evolutionary limit on constructability in synthetic biology," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Duncan Ingram & Guy-Bart Stan, 2023. "Modelling genetic stability in engineered cell populations," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Alicia E. Graham & Rodrigo Ledesma-Amaro, 2023. "The microbial food revolution," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40928-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.