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

Kildegaard KR, Hallström BM, Blicher TH, Sonnenschein N, Jensen NB, Sherstyk S, Harrison SJ, Maury J, HerrgÄrd MJ, Juncker AS, Forster J, Nielsen J, Borodina I

Metab. Eng. 26 (-) 57-66 [2014-11-00; online 2014-09-30]

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.

NGI Stockholm (Genomics Applications)

NGI Stockholm (Genomics Production)

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PubMed 25263954

DOI 10.1016/j.ymben.2014.09.004

Crossref 10.1016/j.ymben.2014.09.004

S1096-7176(14)00118-9