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Coordination of bacterial proteome with metabolism by cyclic AMP signalling

Author

Listed:
  • Conghui You

    (University of California at San Diego
    Section of Molecular Biology, University of California at San Diego)

  • Hiroyuki Okano

    (University of California at San Diego
    Section of Molecular Biology, University of California at San Diego)

  • Sheng Hui

    (University of California at San Diego
    Center for Theoretical Biological Physics, University of California at San Diego)

  • Zhongge Zhang

    (Section of Molecular Biology, University of California at San Diego)

  • Minsu Kim

    (University of California at San Diego)

  • Carl W. Gunderson

    (Section of Molecular Biology, University of California at San Diego)

  • Yi-Ping Wang

    (State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University)

  • Peter Lenz

    (University of Marburg, 35032 Marburg, Germany)

  • Dalai Yan

    (Indiana University School of Medicine)

  • Terence Hwa

    (University of California at San Diego
    Section of Molecular Biology, University of California at San Diego
    Center for Theoretical Biological Physics, University of California at San Diego)

Abstract

The cyclic AMP (cAMP)-dependent catabolite repression effect in Escherichia coli is among the most intensely studied regulatory processes in biology. However, the physiological function(s) of cAMP signalling and its molecular triggers remain elusive. Here we use a quantitative physiological approach to show that cAMP signalling tightly coordinates the expression of catabolic proteins with biosynthetic and ribosomal proteins, in accordance with the cellular metabolic needs during exponential growth. The expression of carbon catabolic genes increased linearly with decreasing growth rates upon limitation of carbon influx, but decreased linearly with decreasing growth rate upon limitation of nitrogen or sulphur influx. In contrast, the expression of biosynthetic genes showed the opposite linear growth-rate dependence as the catabolic genes. A coarse-grained mathematical model provides a quantitative framework for understanding and predicting gene expression responses to catabolic and anabolic limitations. A scheme of integral feedback control featuring the inhibition of cAMP signalling by metabolic precursors is proposed and validated. These results reveal a key physiological role of cAMP-dependent catabolite repression: to ensure that proteomic resources are spent on distinct metabolic sectors as needed in different nutrient environments. Our findings underscore the power of quantitative physiology in unravelling the underlying functions of complex molecular signalling networks.

Suggested Citation

  • Conghui You & Hiroyuki Okano & Sheng Hui & Zhongge Zhang & Minsu Kim & Carl W. Gunderson & Yi-Ping Wang & Peter Lenz & Dalai Yan & Terence Hwa, 2013. "Coordination of bacterial proteome with metabolism by cyclic AMP signalling," Nature, Nature, vol. 500(7462), pages 301-306, August.
    • Handle: RePEc:nat:nature:v:500:y:2013:i:7462:d:10.1038_nature12446
    DOI: 10.1038/nature12446
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    Citations

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    Cited by:

    1. Robert Planqué & Josephus Hulshof & Bas Teusink & Johannes C Hendriks & Frank J Bruggeman, 2018. "Maintaining maximal metabolic flux by gene expression control," PLOS Computational Biology, Public Library of Science, vol. 14(9), pages 1-20, September.
    2. Manlu Zhu & Xiongfeng Dai, 2023. "Stringent response ensures the timely adaptation of bacterial growth to nutrient downshift," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Manlu Zhu & Xiongfeng Dai, 2024. "Shaping of microbial phenotypes by trade-offs," Nature Communications, Nature, vol. 15(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.
    5. Matteo Mori & Chuankai Cheng & Brian R. Taylor & Hiroyuki Okano & Terence Hwa, 2023. "Functional decomposition of metabolism allows a system-level quantification of fluxes and protein allocation towards specific metabolic functions," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Uri Barenholz & Leeat Keren & Eran Segal & Ron Milo, 2016. "A Minimalistic Resource Allocation Model to Explain Ubiquitous Increase in Protein Expression with Growth Rate," PLOS ONE, Public Library of Science, vol. 11(4), pages 1-21, April.
    7. Daphna Rothschild & Erez Dekel & Jean Hausser & Anat Bren & Guy Aidelberg & Pablo Szekely & Uri Alon, 2014. "Linear Superposition and Prediction of Bacterial Promoter Activity Dynamics in Complex Conditions," PLOS Computational Biology, Public Library of Science, vol. 10(5), pages 1-9, May.
    8. Matteo Mori & Vadim Patsalo & Christian Euler & James R. Williamson & Matthew Scott, 2024. "Proteome partitioning constraints in long-term laboratory evolution," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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