Metabolic engineering of Saccharomyces cerevisiae for production of very long chain fatty acid-derived chemicals.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28548095.
- Also identified by DOI 10.1038/ncomms15587 and PMC identifier 5458556.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (C<sub>22</sub>H<sub>46</sub>O) 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<sup>-1</sup> 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.
Medical subject headings
- Fatty Acids
- Fatty Alcohols
- Green Chemistry Technology
- Metabolic Engineering
- Saccharomyces cerevisiae