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dc.contributor.author
Meyer, Fabian
dc.contributor.author
Keller, Philipp
dc.contributor.author
Hartl, Johannes
dc.contributor.author
Gröninger, Olivier G.
dc.contributor.author
Kiefer, Patrick
dc.contributor.author
Vorholt, Julia A.
dc.date.accessioned
2018-04-30T11:23:40Z
dc.date.available
2018-04-27T02:41:18Z
dc.date.available
2018-04-30T11:23:40Z
dc.date.issued
2018
dc.identifier.issn
2041-1723
dc.identifier.other
10.1038/s41467-018-03937-y
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/260951
dc.identifier.doi
10.3929/ethz-b-000260951
dc.description.abstract
Methanol represents an attractive substrate for biotechnological applications. Utilization of reduced one-carbon compounds for growth is currently limited to methylotrophic organisms, and engineering synthetic methylotrophy remains a major challenge. Here we apply an in silico-guided multiple knockout approach to engineer a methanol-essential Escherichia coli strain, which contains the ribulose monophosphate cycle for methanol assimilation. Methanol conversion to biomass was stoichiometrically coupled to the metabolization of gluconate and the designed strain was subjected to laboratory evolution experiments. Evolved strains incorporate up to 24% methanol into core metabolites under a co-consumption regime and utilize methanol at rates comparable to natural methylotrophs. Genome sequencing reveals mutations in genes coding for glutathione-dependent formaldehyde oxidation (frmA), NAD(H) homeostasis/biosynthesis (nadR), phosphopentomutase (deoB), and gluconate metabolism (gntR). This study demonstrates a successful metabolic re-routing linked to a heterologous pathway to achieve methanol-dependent growth and represents a crucial step in generating a fully synthetic methylotrophic organism.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Methanol-essential growth of Escherichia coli
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2018-04-17
ethz.journal.title
Nature Communications
ethz.journal.volume
9
en_US
ethz.journal.abbreviated
Nat Commun
ethz.pages.start
1508
en_US
ethz.size
10 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::03740 - Vorholt, Julia / Vorholt, Julia
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::03740 - Vorholt, Julia / Vorholt, Julia
ethz.date.deposited
2018-04-27T02:41:53Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-04-30T11:23:43Z
ethz.rosetta.lastUpdated
2020-02-15T12:43:38Z
ethz.rosetta.versionExported
true
ethz.COinS
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