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Rewiring native post-transcriptional global regulators to achieve designer, multi-layered genetic circuits

Author

Listed:
  • Trevor R. Simmons

    (The University of Texas at Austin)

  • Gina Partipilo

    (The University of Texas at Austin)

  • Ryan Buchser

    (The University of Texas at Austin)

  • Anna C. Stankes

    (The University of Texas at Austin)

  • Rashmi Srivastava

    (Baylor University)

  • Darian Chiu

    (The University of Texas at Austin)

  • Benjamin K. Keitz

    (The University of Texas at Austin)

  • Lydia M. Contreras

    (The University of Texas at Austin)

Abstract

As synthetic biology expands, creating “drag-and-drop” regulatory tools that can achieve diverse regulatory outcomes are paramount. Herein, we develop a approach for engineering complex post-transcriptional control by rewiring the Carbon Storage Regulatory (Csr) Network of Escherichia coli. We co-opt native interactions of the Csr Network to establish post-transcriptional logic gates and achieve complex bacterial regulation. First, we rationally engineer RNA-protein interactions to create a genetic toolbox of 12 BUFFER Gates that achieves a 15-fold range of expression. Subsequently, we develop a Csr-regulated NOT Gate by integrating a cognate 5’ UTR that is natively Csr-activated into our platform. We then deploy the BUFFER and NOT gates to build a bi-directional regulator, two input Boolean Logic gates OR, NOR, AND and NAND and a pulse-generating circuit. Last, we port our Csr-regulated BUFFER Gate into three industrially relevant bacteria simply by leveraging the conserved Csr Network in each species.

Suggested Citation

  • Trevor R. Simmons & Gina Partipilo & Ryan Buchser & Anna C. Stankes & Rashmi Srivastava & Darian Chiu & Benjamin K. Keitz & Lydia M. Contreras, 2024. "Rewiring native post-transcriptional global regulators to achieve designer, multi-layered genetic circuits," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52976-1
    DOI: 10.1038/s41467-024-52976-1
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    References listed on IDEAS

    as
    1. Yang Gao & Yuchen Zhou & Xudong Ji & Austin J. Graham & Christopher M. Dundas & Ismar E. Miniel Mahfoud & Bailey M. Tibbett & Benjamin Tan & Gina Partipilo & Ananth Dodabalapur & Jonathan Rivnay & Ben, 2024. "A hybrid transistor with transcriptionally controlled computation and plasticity," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Baojun Wang & Richard I Kitney & Nicolas Joly & Martin Buck, 2011. "Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology," Nature Communications, Nature, vol. 2(1), pages 1-9, September.
    3. Jae Sung Cho & Dongsoo Yang & Cindy Pricilia Surya Prabowo & Mohammad Rifqi Ghiffary & Taehee Han & Kyeong Rok Choi & Cheon Woo Moon & Hengrui Zhou & Jae Yong Ryu & Hyun Uk Kim & Sang Yup Lee, 2023. "Targeted and high-throughput gene knockdown in diverse bacteria using synthetic sRNAs," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Anastasia H. Potts & Christopher A. Vakulskas & Archana Pannuri & Helen Yakhnin & Paul Babitzke & Tony Romeo, 2017. "Global role of the bacterial post-transcriptional regulator CsrA revealed by integrated transcriptomics," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    5. Thomas M. Groseclose & Ronald E. Rondon & Zachary D. Herde & Carlos A. Aldrete & Corey J. Wilson, 2020. "Engineered systems of inducible anti-repressors for the next generation of biological programming," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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