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.

Dicarboxylic acid

Multidrug resistance transporter

Adaptive laboratory evolution

Author

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Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Novo Nordisk Foundation Center for Biosustainability

[Person 19f5355c-8e65-4321-b9f2-6f5c4ef01b25 not found]

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

[Person dd04c79b-a128-4db1-b064-f94760d4113e not found]

Technical University of Denmark (DTU)

[Person a5f2fc7f-3368-4331-bf9f-d64369b203b0 not found]

Technical University of Denmark (DTU)

[Person 848afa92-fbaa-4a70-bdcc-d50f6533e5f8 not found]

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

[Person 94defccc-f8f5-4bd9-b278-da00a9a9bc91 not found]

Technical University of Denmark (DTU)

[Person b775baca-9968-4abd-ab21-4290084fcd3f not found]

University of California

Technical University of Denmark (DTU)

[Person 30a8e961-dab2-4813-ad39-14e13c34ac44 not found]

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Technical University of Denmark (DTU)

BioInnovation Institute

[Person cd025e7f-8670-4e3c-9809-cf140bf06e06 not found]

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Metabolic Engineering

1096-7176 (ISSN) 1096-7184 (eISSN)

Vol. 56 130-141

Subject Categories

Biochemistry and Molecular Biology

Other Basic Medicine

Microbiology

DOI

10.1016/j.ymben.2019.09.008

More information

Latest update

11/10/2019