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

被引：0
作者：
Tao Yu
Yongjin J. Zhou
Leonie Wenning
Quanli Liu
Anastasia Krivoruchko
Verena Siewers
Jens Nielsen
Florian David
机构：
[1] Chalmers University of Technology,Department of Biology and Biological Engineering
[2] Novo Nordisk Foundation Center for Biosustainability,undefined
[3] Chalmers University of Technology,undefined
[4] Biopetrolia AB,undefined
[5] Systems and Synthetic Biology Group,undefined
[6] Chalmers University of Technology,undefined
[7] Novo Nordisk Foundation Center for Biosustainability,undefined
[8] Technical University of Denmark,undefined
[9] Science for Life Laboratory,undefined
[10] Royal Institute of Technology,undefined
[11] Present address: Division of Biotechnology,undefined
[12] Dalian Institute of Chemical Physics,undefined
[13] Chinese Academy of Sciences,undefined
[14] Dalian 116023,undefined
[15] China,undefined
来源：
Nature Communications | / 8卷
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摘要：
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.
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