Adaptive laboratory evolution of tolerance to dicarboxylic acids in Saccharomyces cerevisiae.

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ID: 52778
2019
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Abstract
Improving the growth phenotypes of microbes in high product concentrations is an essential design objective in the development of robust cell factories. However, the limited knowledge regarding tolerance mechanisms makes rational design of such traits complicated. Here, adaptive laboratory evolution was used to explore the tolerance mechanisms that Saccharomyces cerevisiae can evolve in the presence of inhibiting concentrations of three dicarboxylic acids: glutaric acid, adipic acid and pimelic acid. Whole-genome sequencing of tolerant mutants enabled the discovery of the genetic changes behind tolerance and most mutations could be linked to the up-regulation of multidrug resistance transporters. The amplification of QDR3, in particular, was shown to confer tolerance not only to the three dicarboxylic acids investigated, but also towards muconic acid and glutaconic acid. In addition to increased acid tolerance, QDR3 overexpression also improved the production of muconic acid in the context of a strain engineered for producing this compound.
Reference Key
pereira2019adaptivemetabolic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Pereira, Rui;Wei, Yongjun;Mohamed, Elsayed;Radi, Mohammad;Malina, Carl;Herrgård, Markus J;Feist, Adam M;Nielsen, Jens;Chen, Yun;
Journal metabolic engineering
Year 2019
DOI
S1096-7176(19)30282-4
URL
Keywords
adaptive laboratory evolution dicarboxylic acid multidrug resistance transporter

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