Adaptive laboratory evolution of tolerance to dicarboxylic acids in Saccharomyces cerevisiae
Journal article, 2019
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.
Adaptive laboratory evolution
Multidrug resistance transporter
Dicarboxylic acid
Author
Rui Pereira
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Novo Nordisk Foundation
Yongjun Wei
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Elsayed Mohamed
Technical University of Denmark (DTU)
Mohammad Radi
Technical University of Denmark (DTU)
Carl Malina
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
M. J. Herrgard
Technical University of Denmark (DTU)
Adam M. Feist
Technical University of Denmark (DTU)
University of California
Jens B Nielsen
Technical University of Denmark (DTU)
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
BioInnovation Institute
Yun Chen
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Metabolic Engineering
1096-7176 (ISSN) 1096-7184 (eISSN)
Vol. 56 130-141Subject Categories (SSIF 2011)
Biochemistry and Molecular Biology
Other Basic Medicine
Microbiology
DOI
10.1016/j.ymben.2019.09.008