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Metabolic engineering of Saccharomyces cerevisiae for production of very long chain fatty acid-derived chemicals

Author

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  • Tao Yu

    (Chalmers University of Technology
    Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology)

  • Yongjin J. Zhou

    (Chalmers University of Technology
    Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology
    Present address: Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China)

  • Leonie Wenning

    (Chalmers University of Technology
    Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology)

  • Quanli Liu

    (Chalmers University of Technology
    Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology)

  • Anastasia Krivoruchko

    (Chalmers University of Technology
    Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology
    Biopetrolia AB, Systems and Synthetic Biology Group, Chalmers University of Technology)

  • Verena Siewers

    (Chalmers University of Technology
    Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology)

  • Jens Nielsen

    (Chalmers University of Technology
    Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology
    Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark
    Science for Life Laboratory, Royal Institute of Technology)

  • Florian David

    (Chalmers University of Technology
    Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology
    Biopetrolia AB, Systems and Synthetic Biology Group, Chalmers University of Technology)

Abstract

Production of chemicals and biofuels through microbial fermentation is an economical and sustainable alternative for traditional chemical synthesis. Here we present the construction of a Saccharomyces cerevisiae platform strain for high-level production of very-long-chain fatty acid (VLCFA)-derived chemicals. Through rewiring the native fatty acid elongation system and implementing a heterologous Mycobacteria FAS I system, we establish an increased biosynthesis of VLCFAs in S. cerevisiae. VLCFAs can be selectively modified towards the fatty alcohol docosanol (C22H46O) by expressing a specific fatty acid reductase. Expression of this enzyme is shown to impair cell growth due to consumption of VLCFA-CoAs. We therefore implement a dynamic control strategy for separating cell growth from docosanol production. We successfully establish high-level and selective docosanol production of 83.5 mg l−1 in yeast. This approach will provide a universal strategy towards the production of similar high value chemicals in a more scalable, stable and sustainable manner.

Suggested Citation

  • Tao Yu & Yongjin J. Zhou & Leonie Wenning & Quanli Liu & Anastasia Krivoruchko & Verena Siewers & Jens Nielsen & Florian David, 2017. "Metabolic engineering of Saccharomyces cerevisiae for production of very long chain fatty acid-derived chemicals," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15587
    DOI: 10.1038/ncomms15587
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    Cited by:

    1. Liu, Zihe & Moradi, Hamideh & Shi, Shuobo & Darvishi, Farshad, 2021. "Yeasts as microbial cell factories for sustainable production of biofuels," Renewable and Sustainable Energy Reviews, Elsevier, vol. 143(C).
    2. M. Tanvir Rahman & M. Kristian Koski & Joanna Panecka-Hofman & Werner Schmitz & Alexander J. Kastaniotis & Rebecca C. Wade & Rik K. Wierenga & J. Kalervo Hiltunen & Kaija J. Autio, 2023. "An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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