Evolution reveals a glutathione-dependent mechanism of 3-hydroxypropionic acid tolerance
Journal article, 2014

Biologically produced 3-hydroxypropionic acid (3HP) is a potential source for sustainable acrylates and can also find direct use as monomer in the production of biodegradable polymers. For industrial scale production there is a need for robust cell factories tolerant to high concentration of 3HP, preferably at low pH. Through adaptive laboratory evolution we selected S. cerevisiae strains with improved tolerance to 3HP at pH 3.5. Genome sequencing followed by functional analysis identified the causal mutation in SFA1 gene encoding S-(hyclroxymerhyl)glutathione dehydrogenase. Based on our findings, we propose that 3HP toxicity is mediated by 3-hydroxypropionic aldehyde (reuterin ) and that glutathione-dependent reactions are used for reuterin detoxification. The identified molecular response to 3HP and reuterin may well be a general mechanism for handling resistance to organic acid and aldehydes by living cells. (C) 2014 International Metabolic Engineering Society Published by Elsevier Inc. On behalf of International Metabolic Engineering Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/)

Adaptive laboratory evolution


3-hydroxypropionic acid

3-hydroxypropionic aldehyde (reuterin)

Saccharomyces cerevisiae


K. R. Kildegaard

Technical University of Denmark (DTU)

B. M. Hallstrom

Royal Institute of Technology (KTH)

T. H. Blicher

University of Copenhagen

N. Sonnenschein

Technical University of Denmark (DTU)

N. B. Jensen

Technical University of Denmark (DTU)

S. Sherstyk

Technical University of Denmark (DTU)

S. J. Harrison

Technical University of Denmark (DTU)

J. Maury

Technical University of Denmark (DTU)

M. J. Herrgard

Technical University of Denmark (DTU)

A. S. Juncker

Technical University of Denmark (DTU)

J. Forster

Technical University of Denmark (DTU)

Jens B Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences

I. Borodina

Technical University of Denmark (DTU)

Metabolic Engineering

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

Vol. 26 57-66

Subject Categories

Industrial Biotechnology

Bioinformatics and Systems Biology

Areas of Advance

Life Science Engineering (2010-2018)



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5/8/2018 1