Journal article
Evolution reveals a glutathione-dependent mechanism of 3-hydroxypropionic acid tolerance
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark1
Research Groups, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark2
KTH Royal Institute of Technology3
University of Copenhagen4
iLoop, Translational Management, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark5
CFB - Core Flow, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark6
Bacterial Cell Factories, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark7
Metagenomics, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark8
Fungal Cell Factories, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark9
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 highconcentration 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-(hydroxymethyl)glutathione dehydrogenase. Based on our findings, we propose that 3HP toxicity is mediated by3-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.
Language: | English |
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Year: | 2014 |
Pages: | 57-66 |
ISSN: | 10967184 and 10967176 |
Types: | Journal article |
DOI: | 10.1016/j.ymben.2014.09.004 |
ORCIDs: | Kildegaard, Kanchana Rueksomtawin , Sonnenschein, Nikolaus , Maury, Jerome , Herrgard, Markus , Förster, Jochen and Borodina, Irina |