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

Kanchana R Kildegaard; Björn M Hallström; Thomas H Blicher; Nikolaus Sonnenschein; Niels B Jensen; Svetlana Sherstyk; Scott J Harrison; Jérôme Maury; Markus J Herrgård; Agnieszka S Juncker; Jochen Forster; Jens Nielsen; Irina Borodina

doi:10.1016/j.ymben.2014.09.004

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

Kanchana R Kildegaard, Björn M Hallström, Thomas H Blicher, Nikolaus Sonnenschein, Niels B Jensen, Svetlana Sherstyk, Scott J Harrison, Jérôme Maury, Markus J Herrgård, Agnieszka S Juncker, Jochen Forster, Jens Nielsen, Irina Borodina

45 Citations (Scopus)

Abstract

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 high concentration 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 by 3-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 language	English
Journal	Metabolic Engineering
Volume	26C
Pages (from-to)	57-66
Number of pages	10
ISSN	1096-7176
DOIs	https://doi.org/10.1016/j.ymben.2014.09.004
Publication status	Published - 1 Nov 2014

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Kildegaard, K. R., Hallström, B. M., Blicher, T. H., Sonnenschein, N., Jensen, N. B., Sherstyk, S., Harrison, S. J., Maury, J., Herrgård, M. J., Juncker, A. S., Forster, J., Nielsen, J., & Borodina, I. (2014). Evolution reveals a glutathione-dependent mechanism of 3-hydroxypropionic acid tolerance. Metabolic Engineering, 26C, 57-66. https://doi.org/10.1016/j.ymben.2014.09.004

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title = "Evolution reveals a glutathione-dependent mechanism of 3-hydroxypropionic acid tolerance",

abstract = "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 high concentration 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 by 3-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.",

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T1 - Evolution reveals a glutathione-dependent mechanism of 3-hydroxypropionic acid tolerance

AU - Kildegaard, Kanchana R

AU - Hallström, Björn M

AU - Blicher, Thomas H

AU - Sonnenschein, Nikolaus

AU - Jensen, Niels B

AU - Sherstyk, Svetlana

AU - Harrison, Scott J

AU - Maury, Jérôme

AU - Herrgård, Markus J

AU - Juncker, Agnieszka S

AU - Forster, Jochen

AU - Nielsen, Jens

AU - Borodina, Irina

PY - 2014/11/1

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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 high concentration 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 by 3-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 high concentration 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 by 3-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.

U2 - 10.1016/j.ymben.2014.09.004

DO - 10.1016/j.ymben.2014.09.004

M3 - Journal article

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SN - 1096-7176

VL - 26C

SP - 57

EP - 66

JO - Metabolic Engineering

JF - Metabolic Engineering

ER -

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

Abstract

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