Adaptive laboratory evolution of tolerance to dicarboxylic acids in Saccharomyces cerevisiae
Artikel i vetenskaplig tidskrift, 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.

Multidrug resistance transporter

Dicarboxylic acid

Adaptive laboratory evolution


Rui Pereira

Chalmers, Biologi och bioteknik, Systembiologi

Novo Nordisk Fonden

Yongjun Wei

Chalmers, Biologi och bioteknik, Systembiologi

Elsayed Mohamed

Danmarks Tekniske Universitet (DTU)

Mohammad Radi

Danmarks Tekniske Universitet (DTU)

Carl Malina

Chalmers, Biologi och bioteknik, Systembiologi

M. J. Herrgard

Danmarks Tekniske Universitet (DTU)

Adam M. Feist

University of California

Danmarks Tekniske Universitet (DTU)

Jens B Nielsen

BioInnovation Institute

Chalmers, Biologi och bioteknik, Systembiologi

Danmarks Tekniske Universitet (DTU)

Yun Chen

Chalmers, Biologi och bioteknik, Systembiologi

Metabolic Engineering

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

Vol. 56 130-141


Biokemi och molekylärbiologi

Annan medicinsk grundvetenskap




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