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)

National Genomics Infrastructure

QC bibliography QC xrefs

PubMed 25263954

DOI 10.1016/j.ymben.2014.09.004

Crossref 10.1016/j.ymben.2014.09.004

S1096-7176(14)00118-9