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An overview and future prospects of recombinant protein production in Bacillus subtilis

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Abstract

Bacillus subtilis is a well-characterized Gram-positive bacterium and a valuable host for recombinant protein production because of its efficient secretion ability, high yield, and non-toxicity. Here, we comprehensively review the recent studies on recombinant protein production in B. subtilis to update and supplement other previous reviews. We have focused on several aspects, including optimization of B. subtilis strains, enhancement and regulation of expression, improvement of secretion level, surface display of proteins, and fermentation optimization. Among them, optimization of B. subtilis strains mainly involves undirected chemical/physical mutagenesis and selection and genetic manipulation; enhancement and regulation of expression comprises autonomous plasmid and integrated expression, promoter regulation and engineering, and fine-tuning gene expression based on proteases and molecular chaperones; improvement of secretion level predominantly involves secretion pathway and signal peptide screening and optimization; surface display of proteins includes surface display of proteins on spores or vegetative cells; and fermentation optimization incorporates medium optimization, process condition optimization, and feeding strategy optimization. Furthermore, we propose some novel methods and future challenges for recombinant protein production in B. subtilis.

Key points

• A comprehensive review on recombinant protein production in Bacillus subtilis.

• Novel techniques facilitate recombinant protein expression and secretion.

• Surface display of proteins has significant potential for different applications.

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Funding

This work was funded by the Key Research and Development Program of China (2021YFC2100200), the Open Project Program of the Key Laboratory of Industrial Biotechnology, Ministry of Education, China (KLIB-KF201907), Natural Science Foundation of Jiangsu Province (BK20191185), and 111 Project (111–2-06).

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Authors and Affiliations

  1. The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China

    Haiquan Yang, Jinfeng Qu, Wei Shen & Xianzhong Chen

  2. College of Bioengineering, Sichuan University of Science & Engineering, Yibin, 644000, Sichuan, China

    Wei Zou

Authors
  1. Haiquan Yang
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  2. Jinfeng Qu
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  3. Wei Zou
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  4. Wei Shen
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  5. Xianzhong Chen
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Contributions

H.Y. and X.C. designed the manuscript. H.Y., J.Q., W.Z., and W.S. wrote the manuscript. H.Y. drew figures. W.S. and X.C. revised the manuscript. All authors read and approved the manuscript.

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Correspondence to Haiquan Yang or Xianzhong Chen.

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Yang, H., Qu, J., Zou, W. et al. An overview and future prospects of recombinant protein production in Bacillus subtilis. Appl Microbiol Biotechnol 105, 6607–6626 (2021). https://doi.org/10.1007/s00253-021-11533-2

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  • DOI: https://doi.org/10.1007/s00253-021-11533-2

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