Global coordination of metabolic pathways in Escherichia coli by active and passive regulation
dc.contributor.author
Kochanowski, Karl
dc.contributor.author
Okano, Hiroyuki
dc.contributor.author
Patsalo, Vadim
dc.contributor.author
Williamson, James
dc.contributor.author
Sauer, Uwe
dc.contributor.author
Hwa, Terence
dc.date.accessioned
2021-04-26T06:25:22Z
dc.date.available
2021-04-25T08:40:17Z
dc.date.available
2021-04-26T06:25:22Z
dc.date.issued
2021-04-01
dc.identifier.issn
1744-4292
dc.identifier.other
10.15252/msb.202010064
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/480368
dc.identifier.doi
10.3929/ethz-b-000480368
dc.description.abstract
Microorganisms adjust metabolic activity to cope with diverse environments. While many studies have provided insights into how individual pathways are regulated, the mechanisms that give rise to coordinated metabolic responses are poorly understood. Here, we identify the regulatory mechanisms that coordinate catabolism and anabolism in Escherichia coli. Integrating protein, metabolite, and flux changes in genetically implemented catabolic or anabolic limitations, we show that combined global and local mechanisms coordinate the response to metabolic limitations. To allocate proteomic resources between catabolism and anabolism, E. coli uses a simple global gene regulatory program. Surprisingly, this program is largely implemented by a single transcription factor, Crp, which directly activates the expression of catabolic enzymes and indirectly reduces the expression of anabolic enzymes by passively sequestering cellular resources needed for their synthesis. However, metabolic fluxes are not controlled by this regulatory program alone; instead, fluxes are adjusted mostly through passive changes in the local metabolite concentrations. These mechanisms constitute a simple but effective global regulatory program that coarsely partitions resources between different parts of metabolism while ensuring robust coordination of individual metabolic reactions.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
EMBO Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
13C flux analysis
en_US
dc.subject
Crp
en_US
dc.subject
metabolomics
en_US
dc.subject
proteomics
en_US
dc.subject
regulation analysis
en_US
dc.title
Global coordination of metabolic pathways in Escherichia coli by active and passive regulation
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2021-04-14
ethz.journal.title
Molecular Systems Biology
ethz.journal.volume
17
en_US
ethz.journal.issue
4
en_US
ethz.journal.abbreviated
Mol Syst Biol
ethz.pages.start
e10064
en_US
ethz.size
14 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Heidelberg
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::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03713 - Sauer, Uwe / Sauer, Uwe
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03713 - Sauer, Uwe / Sauer, Uwe
ethz.date.deposited
2021-04-25T08:40:22Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-04-26T06:25:33Z
ethz.rosetta.lastUpdated
2022-03-29T06:44:44Z
ethz.rosetta.versionExported
true
ethz.COinS
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