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Rational construction of genome-reduced Burkholderiales chassis facilitates efficient heterologous production of natural products from proteobacteria

Author

Listed:
  • Jiaqi Liu

    (Shandong University)

  • Haibo Zhou

    (Shandong University)

  • Zhiyu Yang

    (Shandong University)

  • Xue Wang

    (Shandong University)

  • Hanna Chen

    (Shandong University)

  • Lin Zhong

    (Shandong University)

  • Wentao Zheng

    (Shandong University)

  • Weijing Niu

    (Shandong University)

  • Sen Wang

    (Shandong University)

  • Xiangmei Ren

    (Shandong University)

  • Guannan Zhong

    (Shandong University)

  • Yan Wang

    (Ocean University of China)

  • Xiaoming Ding

    (Fudan University)

  • Rolf Müller

    (Saarland University)

  • Youming Zhang

    (Shandong University)

  • Xiaoying Bian

    (Shandong University)

Abstract

Heterologous expression of biosynthetic gene clusters (BGCs) avails yield improvements and mining of natural products, but it is limited by lacking of more efficient Gram-negative chassis. The proteobacterium Schlegelella brevitalea DSM 7029 exhibits potential for heterologous BGC expression, but its cells undergo early autolysis, hindering further applications. Herein, we rationally construct DC and DT series genome-reduced S. brevitalea mutants by sequential deletions of endogenous BGCs and the nonessential genomic regions, respectively. The DC5 to DC7 mutants affect growth, while the DT series mutants show improved growth characteristics with alleviated cell autolysis. The yield improvements of six proteobacterial natural products and successful identification of chitinimides from Chitinimonas koreensis via heterologous expression in DT mutants demonstrate their superiority to wild-type DSM 7029 and two commonly used Gram-negative chassis Escherichia coli and Pseudomonas putida. Our study expands the panel of Gram-negative chassis and facilitates the discovery of natural products by heterologous expression.

Suggested Citation

  • Jiaqi Liu & Haibo Zhou & Zhiyu Yang & Xue Wang & Hanna Chen & Lin Zhong & Wentao Zheng & Weijing Niu & Sen Wang & Xiangmei Ren & Guannan Zhong & Yan Wang & Xiaoming Ding & Rolf Müller & Youming Zhang , 2021. "Rational construction of genome-reduced Burkholderiales chassis facilitates efficient heterologous production of natural products from proteobacteria," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24645-0
    DOI: 10.1038/s41467-021-24645-0
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    Cited by:

    1. Wentao Zheng & Yuxuan Wang & Jie Cui & Guangyao Guo & Yufeng Li & Jin Hou & Qiang Tu & Yulong Yin & Francis Stewart & Youming Zhang & Xiaoying Bian & Xue Wang, 2024. "ReaL-MGE is a tool for enhanced multiplex genome engineering and application to malonyl-CoA anabolism," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Hanna Chen & Lin Zhong & Haibo Zhou & Xianping Bai & Tao Sun & Xingyan Wang & Yiming Zhao & Xiaoqi Ji & Qiang Tu & Youming Zhang & Xiaoying Bian, 2023. "Biosynthesis and engineering of the nonribosomal peptides with a C-terminal putrescine," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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