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Phosphatase activity tunes two-component system sensor detection threshold

Author

Listed:
  • Brian P. Landry

    (Rice University)

  • Rohan Palanki

    (Rice University)

  • Nikola Dyulgyarov

    (Rice University)

  • Lucas A. Hartsough

    (Rice University)

  • Jeffrey J. Tabor

    (Rice University
    Rice University)

Abstract

Two-component systems (TCSs) are the largest family of multi-step signal transduction pathways in biology, and a major source of sensors for biotechnology. However, the input concentrations to which biosensors respond are often mismatched with application requirements. Here, we utilize a mathematical model to show that TCS detection thresholds increase with the phosphatase activity of the sensor histidine kinase. We experimentally validate this result in engineered Bacillus subtilis nitrate and E. coli aspartate TCS sensors by tuning their detection threshold up to two orders of magnitude. We go on to apply our TCS tuning method to recently described tetrathionate and thiosulfate sensors by mutating a widely conserved residue previously shown to impact phosphatase activity. Finally, we apply TCS tuning to engineer B. subtilis to sense and report a wide range of fertilizer concentrations in soil. This work will enable the engineering of tailor-made biosensors for diverse synthetic biology applications.

Suggested Citation

  • Brian P. Landry & Rohan Palanki & Nikola Dyulgyarov & Lucas A. Hartsough & Jeffrey J. Tabor, 2018. "Phosphatase activity tunes two-component system sensor detection threshold," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03929-y
    DOI: 10.1038/s41467-018-03929-y
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    Cited by:

    1. Stefanie S. M. Meier & Elina Multamäki & Américo T. Ranzani & Heikki Takala & Andreas Möglich, 2024. "Leveraging the histidine kinase-phosphatase duality to sculpt two-component signaling," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Gaurav D. Sankhe & Rubesh Raja & Devendra Pratap Singh & Sneha Bheemireddy & Subinoy Rana & P. J. Athira & Narendra M. Dixit & Deepak Kumar Saini, 2023. "Sequestration of histidine kinases by non-cognate response regulators establishes a threshold level of stimulation for bacterial two-component signaling," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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