Rewiring carbon metabolism in yeast for high level production of aromatic chemicals

Quanli Liu, Tao Yu, Xiaowei Li, Yu Chen, Kate Campbell, Jens Nielsen and Yun Chen ()
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Quanli Liu: Chalmers University of Technology
Tao Yu: Chalmers University of Technology
Xiaowei Li: Chalmers University of Technology
Yu Chen: Chalmers University of Technology
Kate Campbell: Chalmers University of Technology
Jens Nielsen: Chalmers University of Technology
Yun Chen: Chalmers University of Technology

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract The production of bioactive plant compounds using microbial hosts is considered a safe, cost-competitive and scalable approach to their production. However, microbial production of some compounds like aromatic amino acid (AAA)-derived chemicals, remains an outstanding metabolic engineering challenge. Here we present the construction of a Saccharomyces cerevisiae platform strain able to produce high levels of p-coumaric acid, an AAA-derived precursor for many commercially valuable chemicals. This is achieved through engineering the AAA biosynthesis pathway, introducing a phosphoketalose-based pathway to divert glycolytic flux towards erythrose 4-phosphate formation, and optimizing carbon distribution between glycolysis and the AAA biosynthesis pathway by replacing the promoters of several important genes at key nodes between these two pathways. This results in a maximum p-coumaric acid titer of 12.5 g L−1 and a maximum yield on glucose of 154.9 mg g−1.

Date: 2019
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DOI: 10.1038/s41467-019-12961-5

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