TY - JOUR
T1 - Evolution reveals a glutathione-dependent mechanism of 3-hydroxypropionic acid tolerance
AU - Kildegaard, Kanchana Rueksomtawin
AU - Hallström, Björn M.
AU - Blicher, Thomas H.
AU - Sonnenschein, Nikolaus
AU - Jensen, Niels Bjerg
AU - Sherstyk, Svetlana
AU - Harrison, Scott James
AU - Maury, Jerome
AU - Herrgard, Markus
AU - Juncker, Agnieszka
AU - Förster, Jochen
AU - Nielsen, Jens
AU - Borodina, Irina
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - 3-hydroxypropionic acid
KW - Tolerance
KW - 3-hydroxypropionic aldehyde (reuterin)
KW - Saccharomyces cerevisiae
KW - Adaptive laboratory evolution
U2 - 10.1016/j.ymben.2014.09.004
DO - 10.1016/j.ymben.2014.09.004
M3 - Journal article
C2 - 25263954
SN - 1096-7176
VL - 26
SP - 57
EP - 66
JO - Metabolic Engineering
JF - Metabolic Engineering
ER -