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Tuning the dynamic range of bacterial promoters regulated by ligand-inducible transcription factors

Author

Listed:
  • Ye Chen

    (Rice University)

  • Joanne M. L. Ho

    (Rice University)

  • David L. Shis

    (Rice University)

  • Chinmaya Gupta

    (University of Houston)

  • James Long

    (Rice University)

  • Daniel S. Wagner

    (Rice University)

  • William Ott

    (University of Houston)

  • Krešimir Josić

    (Rice University
    University of Houston
    University of Houston)

  • Matthew R. Bennett

    (Rice University
    Rice University)

Abstract

One challenge for synthetic biologists is the predictable tuning of genetic circuit regulatory components to elicit desired outputs. Gene expression driven by ligand-inducible transcription factor systems must exhibit the correct ON and OFF characteristics: appropriate activation and leakiness in the presence and absence of inducer, respectively. However, the dynamic range of a promoter (i.e., absolute difference between ON and OFF states) is difficult to control. We report a method that tunes the dynamic range of ligand-inducible promoters to achieve desired ON and OFF characteristics. We build combinatorial sets of AraC-and LasR-regulated promoters containing −10 and −35 sites from synthetic and Escherichia coli promoters. Four sequence combinations with diverse dynamic ranges were chosen to build multi-input transcriptional logic gates regulated by two and three ligand-inducible transcription factors (LacI, TetR, AraC, XylS, RhlR, LasR, and LuxR). This work enables predictable control over the dynamic range of regulatory components.

Suggested Citation

  • Ye Chen & Joanne M. L. Ho & David L. Shis & Chinmaya Gupta & James Long & Daniel S. Wagner & William Ott & Krešimir Josić & Matthew R. Bennett, 2018. "Tuning the dynamic range of bacterial promoters regulated by ligand-inducible transcription factors," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02473-5
    DOI: 10.1038/s41467-017-02473-5
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    Cited by:

    1. Shivang Hina-Nilesh Joshi & Chentao Yong & Andras Gyorgy, 2022. "Inducible plasmid copy number control for synthetic biology in commonly used E. coli strains," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Charlotte Cautereels & Jolien Smets & Peter Bircham & Dries De Ruysscher & Anna Zimmermann & Peter De Rijk & Jan Steensels & Anton Gorkovskiy & Joleen Masschelein & Kevin J. Verstrepen, 2024. "Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Chenrui Qin & Yanhui Xiang & Jie Liu & Ruilin Zhang & Ziming Liu & Tingting Li & Zhi Sun & Xiaoyi Ouyang & Yeqing Zong & Haoqian M. Zhang & Qi Ouyang & Long Qian & Chunbo Lou, 2023. "Precise programming of multigene expression stoichiometry in mammalian cells by a modular and programmable transcriptional system," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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