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Repurposing endogenous type I-E CRISPR-Cas systems for natural product discovery in Streptomyces

Author

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  • Qun Zhou

    (School of Chemical Engineering and Technology, Tianjin University
    Haihe Laboratory of Sustainable Chemical Transformations)

  • Yatong Zhao

    (School of Chemical Engineering and Technology, Tianjin University
    Haihe Laboratory of Sustainable Chemical Transformations)

  • Changqiang Ke

    (Chinese Academy of Sciences)

  • Haojun Wang

    (Sichuan University)

  • Sheng Gao

    (Sichuan University)

  • Hui Li

    (Sichuan University)

  • Yan Zhang

    (School of Chemical Engineering and Technology, Tianjin University
    Tianjin University)

  • Yang Ye

    (Chinese Academy of Sciences)

  • Yunzi Luo

    (School of Chemical Engineering and Technology, Tianjin University
    Haihe Laboratory of Sustainable Chemical Transformations
    Nanshan District)

Abstract

The multifunctional proteins of class 2 CRISPR systems such as Cas9, have been employed to activate cryptic biosynthetic gene clusters (BGCs) in Streptomyces, which represent a large and hidden reservoir of natural products. However, such approaches are not applicable to most Streptomyces strains with reasons to be comprehended. Inspired by the prevalence of the class 1 subtype especially the type I-E CRISPR system in Streptomyces, here we report the development of the type I-E CRISPR system into a series of transcriptional regulation tools. We further demonstrate the effectiveness of such activators in nine phylogenetically distant Streptomyces strains. Using these tools, we successfully activate 13 out of 21 BGCs and lead to the identification and characterization of one polyketide, one Ripp and three alkaloid products. Our work is expected to have a profound impact and to facilitate the discovery of numerous structurally diverse compounds from Streptomyces.

Suggested Citation

  • Qun Zhou & Yatong Zhao & Changqiang Ke & Haojun Wang & Sheng Gao & Hui Li & Yan Zhang & Yang Ye & Yunzi Luo, 2024. "Repurposing endogenous type I-E CRISPR-Cas systems for natural product discovery in Streptomyces," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54196-z
    DOI: 10.1038/s41467-024-54196-z
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    References listed on IDEAS

    as
    1. Wenjun Jiang & Xuejin Zhao & Tslil Gabrieli & Chunbo Lou & Yuval Ebenstein & Ting F. Zhu, 2015. "Cas9-Assisted Targeting of CHromosome segments CATCH enables one-step targeted cloning of large gene clusters," Nature Communications, Nature, vol. 6(1), pages 1-8, November.
    2. Chen Dong & Jason Fontana & Anika Patel & James M. Carothers & Jesse G. Zalatan, 2018. "Synthetic CRISPR-Cas gene activators for transcriptional reprogramming in bacteria," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
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    4. Yunzi Luo & Hua Huang & Jing Liang & Meng Wang & Lu Lu & Zengyi Shao & Ryan E. Cobb & Huimin Zhao, 2013. "Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster," Nature Communications, Nature, vol. 4(1), pages 1-8, December.
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