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Systematic identification of metabolites controlling gene expression in E. coli

Author

Listed:
  • Martin Lempp

    (Max Planck Institute for Terrestrial Microbiology)

  • Niklas Farke

    (Max Planck Institute for Terrestrial Microbiology)

  • Michelle Kuntz

    (Max Planck Institute for Terrestrial Microbiology)

  • Sven Andreas Freibert

    (Philipps-Universität Marburg)

  • Roland Lill

    (Philipps-Universität Marburg
    Philipps-Universität Marburg)

  • Hannes Link

    (Max Planck Institute for Terrestrial Microbiology
    Philipps-Universität Marburg)

Abstract

Metabolism controls gene expression through allosteric interactions between metabolites and transcription factors. These interactions are usually measured with in vitro assays, but there are no methods to identify them at a genome-scale in vivo. Here we show that dynamic transcriptome and metabolome data identify metabolites that control transcription factors in E. coli. By switching an E. coli culture between starvation and growth, we induce strong metabolite concentration changes and gene expression changes. Using Network Component Analysis we calculate the activities of 209 transcriptional regulators and correlate them with metabolites. This approach captures, for instance, the in vivo kinetics of CRP regulation by cyclic-AMP. By testing correlations between all pairs of transcription factors and metabolites, we predict putative effectors of 71 transcription factors, and validate five interactions in vitro. These results show that combining transcriptomics and metabolomics generates hypotheses about metabolism-transcription interactions that drive transitions between physiological states.

Suggested Citation

  • Martin Lempp & Niklas Farke & Michelle Kuntz & Sven Andreas Freibert & Roland Lill & Hannes Link, 2019. "Systematic identification of metabolites controlling gene expression in E. coli," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12474-1
    DOI: 10.1038/s41467-019-12474-1
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    Cited by:

    1. Gaoyang Li & Li Liu & Wei Du & Huansheng Cao, 2023. "Local flux coordination and global gene expression regulation in metabolic modeling," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Enrico Orsi & Pablo Ivan Nikel & Lars Keld Nielsen & Stefano Donati, 2023. "Synergistic investigation of natural and synthetic C1-trophic microorganisms to foster a circular carbon economy," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    3. Yichao Han & Wanji Li & Alden Filko & Jingyao Li & Fuzhong Zhang, 2023. "Genome-wide promoter responses to CRISPR perturbations of regulators reveal regulatory networks in Escherichia coli," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Ida Lauritsen & Pernille Ott Frendorf & Silvia Capucci & Sophia A. H. Heyde & Sarah D. Blomquist & Sofie Wendel & Emil C. Fischer & Agnieszka Sekowska & Antoine Danchin & Morten H. H. Nørholm, 2021. "Temporal evolution of master regulator Crp identifies pyrimidines as catabolite modulator factors," Nature Communications, Nature, vol. 12(1), pages 1-13, December.

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