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A robust yeast biocontainment system with two-layered regulation switch dependent on unnatural amino acid

Author

Listed:
  • Tiantian Chang

    (University of Chinese Academy of Sciences
    BGI Research)

  • Weichao Ding

    (University of Chinese Academy of Sciences
    BGI Research
    BGI Research
    Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research)

  • Shirui Yan

    (BGI Research
    BGI Research
    Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research)

  • Yun Wang

    (BGI Research
    BGI Research
    Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research)

  • Haoling Zhang

    (BGI Research
    BGI Research
    Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research)

  • Yu Zhang

    (BGI Research
    Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research)

  • Zhi Ping

    (BGI Research
    BGI Research
    Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research)

  • Huiming Zhang

    (University of Chinese Academy of Sciences
    BGI Research)

  • Yijian Huang

    (University of Chinese Academy of Sciences
    BGI Research)

  • Jiahui Zhang

    (University of Chinese Academy of Sciences
    BGI Research)

  • Dan Wang

    (Guangdong Provincial Key Laboratory of Interdisciplinary Research and Application for Data Science, BNU-HKBU United International College
    BNU-HKBU United International College)

  • Wenwei Zhang

    (BGI Research
    Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research)

  • Xun Xu

    (BGI Research
    BGI Research
    Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research)

  • Yue Shen

    (University of Chinese Academy of Sciences
    BGI Research
    BGI Research
    Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research)

  • Xian Fu

    (BGI Research
    BGI Research
    Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research)

Abstract

Synthetic auxotrophy in which cell viability depends on the presence of an unnatural amino acid (unAA) provides a powerful strategy to restrict unwanted propagation of genetically modified organisms (GMOs) in open environments and potentially prevent industrial espionage. Here, we describe a generic approach for robust biocontainment of budding yeast dependent on unAA. By understanding escape mechanisms, we specifically optimize our strategies by introducing designed “immunity” to the generation of amber-suppressor tRNAs and developing the transcriptional- and translational-based biocontainment switch. We further develop a fitness-oriented screening method to easily obtain multiplex safeguard strains that exhibit robust growth and undetectable escape frequency (

Suggested Citation

  • Tiantian Chang & Weichao Ding & Shirui Yan & Yun Wang & Haoling Zhang & Yu Zhang & Zhi Ping & Huiming Zhang & Yijian Huang & Jiahui Zhang & Dan Wang & Wenwei Zhang & Xun Xu & Yue Shen & Xian Fu, 2023. "A robust yeast biocontainment system with two-layered regulation switch dependent on unnatural amino acid," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42358-4
    DOI: 10.1038/s41467-023-42358-4
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    References listed on IDEAS

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    Cited by:

    1. Stefan A. Hoffmann & Yizhi Cai, 2024. "Engineering stringent genetic biocontainment of yeast with a protein stability switch," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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