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Metabolic engineering of Saccharomyces cerevisiae for production of very long chain fatty acid-derived chemicals
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, 15587Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017. Vol. 8, 15587
National Category
Biocatalysis and Enzyme Technology
Identifiers
URN: urn:nbn:se:kth:diva-208719DOI: 10.1038/ncomms15587ISI: 000402047300001PubMedID: 28548095Scopus ID: 2-s2.0-85020019811OAI: oai:DiVA.org:kth-208719DiVA: diva2:1108395
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20170612

Available from: 2017-06-12 Created: 2017-06-12 Last updated: 2017-06-22Bibliographically approved

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Nielsen, Jens

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