MassIVE MSV000086992

Complete Public PXD024504

Global coordination of metabolic pathways in Escherichia coli by active and passive regulation

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Description

In this study, we identify the regulatory mechanisms that coordinate catabolism and anabolism in the bacterium Escherichia coli. Integrating protein, metabolite, and metabolic flux changes in genetically implemented gradual catabolic or anabolic limitations, we show that a combination of global and local mechanisms coordinates 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 not only directly activates the expression of catabolic enzymes, but also indirectly reduces the expression of anabolic enzymes by passively sequestering cellular resources needed for their synthesis. However, this regulatory program rarely controls metabolic fluxes alone; instead, fluxes are further adjusted locally through passive changes in metabolite concentrations. Together, these mechanisms constitute a limited but effective global regulatory program that coarsely partitions resources between different parts of metabolism while ensuring the robust coordination of individual metabolic reactions. [doi:10.25345/C5TB9T] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: cAMP ; gene expression ; growth laws ; regulation ; cyclic AMP ; gene regulation ; transcription

Contact

Principal Investigators:
(in alphabetical order) 		James R. Williamson, The Scripps Research Institute, United States
Karl Kochanowski, ETH Zurich, Switzerland
Terence Hwa, UC San Diego, United States
Uwe Sauer, ETH Zurich, Switzerland
Submitting User: patsalo

Publications

Kochanowski K, Okano H, Patsalo V, Williamson J, Sauer U, Hwa T.
Global coordination of metabolic pathways in Escherichia coli by active and passive regulation.
Mol Syst Biol. 2021 Apr;17(4):e10064.

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