Evolution reveals a glutathione-dependent mechanism of 3-hydroxypropionic acid tolerance

Kanchana Rueksomtawin Kildegaard, Björn M. Hallström, Thomas H. Blicher, Nikolaus Sonnenschein, Niels Bjerg Jensen, Svetlana Sherstyk, Scott James Harrison, Jerome Maury, Markus Herrgard, Agnieszka Juncker, Jochen Förster, Jens Nielsen, Irina Borodina

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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.
Original languageEnglish
JournalMetabolic Engineering
Pages (from-to)57-66
Number of pages10
Publication statusPublished - 2014


  • 3-hydroxypropionic acid
  • Tolerance
  • 3-hydroxypropionic aldehyde (reuterin)
  • Saccharomyces cerevisiae
  • Adaptive laboratory evolution

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