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Evolution reveals a glutathione-dependent mechanism of 3-hydroxypropionic acid tolerance
Kanchana R Kildegaard1, Björn M Hallström2, Thomas H Blicher3
1The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé 6, DK-2970 Hørsholm, Denmark.
Abstract:
Biologically produced 3-hydroxypropionic acid (3 HP) 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 3 HP, preferably at low pH. Through adaptive laboratory evolution we selected S. cerevisiae strains with improved tolerance to 3 HP 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 3 HP toxicity is mediated by 3-hydroxypropionic aldehyde (reuterin) and that glutathione-dependent reactions are used for reuterin detoxification. The identified molecular response to 3 HP and reuterin may well be a general mechanism for handling resistance to organic acid and aldehydes by living cells.
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