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Improvement of tacrolimus production in Streptomyces tsukubaensis by mutagenesis and optimization of fermentation medium using Plackett–Burman design combined with response surface methodology

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Abstract

Objective

This study was conducted to enhance the production of tacrolimus in Streptomyces tsukubaensis by strain mutagenesis and optimization of the fermentation medium.

Results

A high tacrolimus producing strain S. tsukubaensis FIM-16-06 was obtained by ultraviolet mutagenesis coupled with atmospheric and room temperature plasma mutagenesis.Then, nine variables were screened using Plackett–Burman experimental design, in which soluble starch, peptone and Tween 80 showed significantly affected tacrolimus production. Further studies were carried out employing central composite design to elucidate the mutual interaction between the variables and to work out optimal fermentation medium composition for tacrolimus production. The optimum fermentation medium was found to contain 61.61 g/L of soluble starch, 20.61 g/L of peptone and 30.79 g/L of Tween 80. In the optimized medium, the production of tacrolimus reached 1293 mg/L in shake-flask culture, and reached 1522 mg/L while the scaled-up fermentation was conducted in a 1000 L fermenter, which was about 3.7 times higher than that in the original medium.

Conclusions

Combining compound mutation with rational medium optimization is an effective approach for improving tacrolimus production, and the optimized fermentation medium could be efficiently used for industrial production.

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Funding

This work was supported by Special Project of Public Welfare Research Institute of Fujian Province of China (Grant Nos. 2019R1005-8 and 2020R1005009). The funders had no role in study design, data collection, and interpretation of results or manuscript writing.

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Authors and Affiliations

  1. Fujian Provincial Key Laboratory of Screening for Novel Microbial Products, Fujian Institute of Microbiology, Fuzhou, 350007, China

    Lingbin Yan, Zhulan Zhang, Yin Zhang, Huangjian Yang, Guanrong Qiu, Desen Wang & Yunyang Lian

Authors
  1. Lingbin Yan
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  2. Zhulan Zhang
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  3. Yin Zhang
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  4. Huangjian Yang
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  5. Guanrong Qiu
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  7. Yunyang Lian
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Contributions

LY designed the research and prepared the manuscript. YL and ZZ supervised the research work and guided the experimental design. YZ, HY, DW and GQ provided the suggestion of the research work. All authors contributed to interpretation of the results and manuscript drafting. All authors read and approved the final manuscript.

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Correspondence to Zhulan Zhang or Yunyang Lian.

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Yan, L., Zhang, Z., Zhang, Y. et al. Improvement of tacrolimus production in Streptomyces tsukubaensis by mutagenesis and optimization of fermentation medium using Plackett–Burman design combined with response surface methodology. Biotechnol Lett 43, 1765–1778 (2021). https://doi.org/10.1007/s10529-021-03144-8

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  • DOI: https://doi.org/10.1007/s10529-021-03144-8

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