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

Tao Yu (Institutionen för biologi och bioteknik, Systembiologi) ; Yongjin Zhou (Institutionen för biologi och bioteknik, Systembiologi) ; Leonie Wenning (Institutionen för biologi och bioteknik, Systembiologi) ; Quanli Liu (Institutionen för biologi och bioteknik, Systembiologi) ; Anastasia Krivoruchko (Institutionen för biologi och bioteknik, Systembiologi) ; Verena Siewers (Institutionen för biologi och bioteknik, Systembiologi) ; Jens B. Nielsen (Institutionen för biologi och bioteknik, Systembiologi) ; Florian David (Institutionen för biologi och bioteknik, Systembiologi)
Nature Communications (2041-1723). Vol. 8 (2017), p. Article number: 15587.
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: genetic modifications, acetyl-coenzyme, jojoba oil, yeast, pathway, elongation, biosynthesis, synthase, arabidopsis, reductases, Science & Technology - Other Topics



Denna post skapades 2017-07-12.
CPL Pubid: 250641

 

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Institutioner (Chalmers)

Institutionen för biologi och bioteknik, Systembiologi

Ämnesområden

Bioinformatik och systembiologi

Chalmers infrastruktur