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

Dicarboxylic Acids / pharmacology Directed Molecular Evolution Gene Expression Regulation, Fungal Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae Proteins / biosynthesis
Adaptive laboratory evolution Dicarboxylic acid Multidrug resistance transporter

Journal

Metabolic engineering
ISSN: 1096-7184
Titre abrégé: Metab Eng
Pays: Belgium
ID NLM: 9815657

Informations de publication

Date de publication:
12 2019
Historique:
received: 16 07 2019
revised: 19 09 2019
accepted: 19 09 2019
pubmed: 25 9 2019
medline: 23 4 2020
entrez: 25 9 2019
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.ymben.2019.09.008 PMID: 31550508
pubmed: 31550508
pii: S1096-7176(19)30282-4
doi: 10.1016/j.ymben.2019.09.008
pii:
doi:

Substances chimiques

Dicarboxylic Acids 0
Saccharomyces cerevisiae Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

130-141

Informations de copyright

Copyright © 2019 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Auteurs

Rui Pereira (R)

Department of Biology and Biological Engineering, Chalmers University of Technology, 41296, Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, 41296, Gothenburg, Sweden.

Yongjun Wei (Y)

Department of Biology and Biological Engineering, Chalmers University of Technology, 41296, Gothenburg, Sweden.

Elsayed Mohamed (E)

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet, 2800, Kgs. Lyngby, Denmark.

Mohammad Radi (M)

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet, 2800, Kgs. Lyngby, Denmark.

Carl Malina (C)

Department of Biology and Biological Engineering, Chalmers University of Technology, 41296, Gothenburg, Sweden.

Markus J Herrgård (MJ)

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet, 2800, Kgs. Lyngby, Denmark.

Adam M Feist (AM)

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet, 2800, Kgs. Lyngby, Denmark; Department of Bioengineering, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA, 92093, USA.

Jens Nielsen (J)

Department of Biology and Biological Engineering, Chalmers University of Technology, 41296, Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, 41296, Gothenburg, Sweden; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet, 2800, Kgs. Lyngby, Denmark; BioInnovation Institute, Ole Maaløes Vej 3, DK2200, Copenhagen N, Denmark.

Yun Chen (Y)

Department of Biology and Biological Engineering, Chalmers University of Technology, 41296, Gothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, 41296, Gothenburg, Sweden. Electronic address: yunc@chalmers.se.

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Classifications MeSH

questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Acides acycliques › Diacides carboxyliques › Adaptive laboratory evolution of tolerance to...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Évolution moléculaire dirigée › Adaptive laboratory evolution of tolerance to...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes fongiques › Adaptive laboratory evolution of tolerance to...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Saccharomyces › Saccharomyces cerevisiae › Adaptive laboratory evolution of tolerance to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines fongiques › Protéines de Saccharomyces cerevisiae › Adaptive laboratory evolution of tolerance to...