Multi-omics Analysis of CRISPRi-Knockdowns Identifies Mechanisms that Buffer Decreases of Enzymes in E. coli Metabolism

Stefano Donati; Michelle Kuntz; Vanessa Pahl; Niklas Farke; Dominik Beuter; Timo Glatter; José Vicente Gomes-Filho; Lennart Randau; Chun Ying Wang; Hannes Link

doi:10.1016/j.cels.2020.10.011

Multi-omics Analysis of CRISPRi-Knockdowns Identifies Mechanisms that Buffer Decreases of Enzymes in E. coli Metabolism

Stefano Donati, Michelle Kuntz, Vanessa Pahl, Niklas Farke, Dominik Beuter, Timo Glatter, José Vicente Gomes-Filho, Lennart Randau, Chun Ying Wang, Hannes Link^*

^*Corresponding author for this work

Novo Nordisk Foundation Center for Biosustainability

Max Planck Institute for Terrestrial Microbiology

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Abstract

Donati and Kuntz et al., study the consequences of CRISPR interference in Escherichia coli metabolism. Their work suggests that metabolism is robust against knockdowns of enzymes and that regulatory metabolite-protein interactions buffer such perturbations.

Original language	English
Journal	Cell Systems
Volume	12
Issue number	1
Pages (from-to)	56-67.e6
ISSN	2405-4712
DOIs	https://doi.org/10.1016/j.cels.2020.10.011
Publication status	Published - 20 Jan 2021

Bibliographical note

Funding Information:
We thank T.J. Erb, V. Sourjik, and A. Diepold for discussions. We thank J. Elf for providing the YYdCas9 strain. This work has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 715650, ERC Starting Grant MapMe). S.D. and M.K. acknowledge funding from the IMPRS graduate school for environmental, cellular, and molecular microbiology from the Max Planck Society. L.R. acknowledges funding from DFG SPP2141. S.D. performed experiments with arrayed CRISPRi strains, analyzed data, performed FBA analysis, and co-wrote the manuscript. M.K. performed experiments with the pooled CRISPRi library and co-wrote the manuscript. M.K. and S.D. analyzed data from the pooled CRISPRi screen. V.P. performed experiments with arrayed CRISPRi strains. N.F. developed and analyzed the CarAB model. D.B. constructed the pooled CRISPRi library. M.K. J.V.G.F. and L.R. performed Illumina sequencing. T.G. measured proteomes. C.-Y.W. performed experiments. H.L. conceived the study, analyzed data, and co-wrote the manuscript. The authors declare no competing interests.

Publisher Copyright:
© 2020 The Authors

Keywords

Allosteric regulation
CRISPR interference
Metabolic robustness
Metabolomics
Proteomics
Transcriptional regulation

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title = "Multi-omics Analysis of CRISPRi-Knockdowns Identifies Mechanisms that Buffer Decreases of Enzymes in E. coli Metabolism",

abstract = "Donati and Kuntz et al., study the consequences of CRISPR interference in Escherichia coli metabolism. Their work suggests that metabolism is robust against knockdowns of enzymes and that regulatory metabolite-protein interactions buffer such perturbations.",

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AU - Beuter, Dominik

AU - Glatter, Timo

AU - Gomes-Filho, José Vicente

AU - Randau, Lennart

AU - Wang, Chun Ying

AU - Link, Hannes

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Multi-omics Analysis of CRISPRi-Knockdowns Identifies Mechanisms that Buffer Decreases of Enzymes in E. coli Metabolism

Abstract

Bibliographical note

Keywords

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