Journal
BIOTECHNOLOGY LETTERS
Volume 43, Issue 9, Pages 1765-1778Publisher
SPRINGER
DOI: 10.1007/s10529-021-03144-8
Keywords
Central composite design; Fermentation medium; Plackett– Burman design; Tacrolimus; Tween 80
Categories
Funding
- Special Project of Public Welfare Research Institute of Fujian Province of China [2019R1005-8, 2020R1005009]
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This study successfully enhanced the production of tacrolimus in Streptomyces tsukubaensis through strain mutagenesis and optimization of the fermentation medium. The high tacrolimus producing strain S. tsukubaensis FIM-16-06 was obtained, and optimal fermentation medium composition was determined, leading to a significant increase in tacrolimus production.
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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