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

Tao Yu, Yongjin J. Zhou, Leonie Wenning, Quanli Liu, Anastasia Krivoruchko, Verena Siewers, Jens Nielsen and Florian David ()
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Tao Yu: Chalmers University of Technology
Yongjin J. Zhou: Chalmers University of Technology
Leonie Wenning: Chalmers University of Technology
Quanli Liu: Chalmers University of Technology
Anastasia Krivoruchko: Chalmers University of Technology
Verena Siewers: Chalmers University of Technology
Jens Nielsen: Chalmers University of Technology
Florian David: Chalmers University of Technology

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15587

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DOI: 10.1038/ncomms15587

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