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Programmable biomolecular switches for rewiring flux in Escherichia coli

Author

Listed:
  • Cong Gao

    (Jiangnan University
    Jiangnan University)

  • Jianshen Hou

    (Jiangnan University
    Jiangnan University)

  • Peng Xu

    (University of Maryland Baltimore County)

  • Liang Guo

    (Jiangnan University
    Jiangnan University)

  • Xiulai Chen

    (Jiangnan University
    Jiangnan University)

  • Guipeng Hu

    (Jiangnan University
    Jiangnan University)

  • Chao Ye

    (Jiangnan University
    Jiangnan University)

  • Harley Edwards

    (University of Maryland Baltimore County)

  • Jian Chen

    (Jiangnan University)

  • Wei Chen

    (Jiangnan University)

  • Liming Liu

    (Jiangnan University
    Jiangnan University
    Jiangnan University)

Abstract

Synthetic biology aims to develop programmable tools to perform complex functions such as redistributing metabolic flux in industrial microorganisms. However, development of protein-level circuits is limited by availability of designable, orthogonal, and composable tools. Here, with the aid of engineered viral proteases and proteolytic signals, we build two sets of controllable protein units, which can be rationally configured to three tools. Using a protease-based dynamic regulation circuit to fine-tune metabolic flow, we achieve 12.63 g L−1 shikimate titer in minimal medium without inducer. In addition, the carbon catabolite repression is alleviated by protease-based inverter-mediated flux redistribution under multiple carbon sources. By coordinating reaction rate using a protease-based oscillator in E. coli, we achieve d-xylonate productivity of 7.12 g L−1 h−1 with a titer of 199.44 g L−1. These results highlight the applicability of programmable protein switches to metabolic engineering for valuable chemicals production.

Suggested Citation

  • Cong Gao & Jianshen Hou & Peng Xu & Liang Guo & Xiulai Chen & Guipeng Hu & Chao Ye & Harley Edwards & Jian Chen & Wei Chen & Liming Liu, 2019. "Programmable biomolecular switches for rewiring flux in Escherichia coli," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11793-7
    DOI: 10.1038/s41467-019-11793-7
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    Cited by:

    1. Wenwen Diao & Liang Guo & Qiang Ding & Cong Gao & Guipeng Hu & Xiulai Chen & Yang Li & Linpei Zhang & Wei Chen & Jian Chen & Liming Liu, 2021. "Reprogramming microbial populations using a programmed lysis system to improve chemical production," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Yuanli Gao & Lei Wang & Baojun Wang, 2023. "Customizing cellular signal processing by synthetic multi-level regulatory circuits," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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