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, high titer,
rate and yield are essential; thus 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 of three independent
clones identified single-nucleotide changes in the
SFA1 gene encoding S-(hydroxymethyl)glutathione dehydrogenase.
Introduction of the mutated SFA1 alleles or
overexpression of any of the SFA1 alleles in a sfa16 strain
enabled growth in the presence of above 40 g/L 3HP.
We further found that aldehyde dehydrogenase (ALD6),
S-formylglutathione hydrolase (YJL068C) and glutathione
play a role in 3HP detoxicification. Addition of glutathione
relieved growth inhibition by 3HP for several yeast species
and for E. coli; but glutathione could not enable growth of
a S. cerevisiae sfa16 strain. Based on our findings we propose
a 3-hydroxypropionic aldehyde-mediated mechanism
underlying 3HP toxicity as well as a glutathione-dependent
route for detoxification of 3-hydroxypropionic aldehyde
(reuterin). The identified molecular response to 3HP and
reuterin may well be a general mechanism for handling
resistance to organic acids and aldehydes by living cells
Original language | English |
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Publication date | 2014 |
Number of pages | 1 |
Publication status | Published - 2014 |
Event | Metabolic Engineering X: Biological Design and Synthesis - Vancouver, Canada Duration: 15 Jun 2014 → 19 Jun 2014 |
Conference
Conference | Metabolic Engineering X |
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Country/Territory | Canada |
City | Vancouver |
Period | 15/06/2014 → 19/06/2014 |