Improvement of FK506 production by selection of 4-Aminobutyric acid-tolerant mutant and optimization of its fermentation using response surface methodology
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  • 作者:Tianyi Yang (1)
    Jiaojiao Li (1)
    Liangzhi Li (1) (2)
    Haiyang Zhang (1)
    Jing Ma (1)
    Zhi Chen (1)
    Cuiying Hu (1)
    Xin Ju (1)
    Jiaolong Fu (1)
  • 关键词:4 ; Aminobutyric acid ; mutant ; response surface methodology ; Streptomyces tsukubaensis ; tacrolimus
  • 刊名:Journal of the Korean Society for Applied Biological Chemistry
  • 出版年:2014
  • 出版时间:December 2014
  • 年:2014
  • 卷:57
  • 期:6
  • 页码:715-722
  • 全文大小:293 KB
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  • 作者单位:Tianyi Yang (1)
    Jiaojiao Li (1)
    Liangzhi Li (1) (2)
    Haiyang Zhang (1)
    Jing Ma (1)
    Zhi Chen (1)
    Cuiying Hu (1)
    Xin Ju (1)
    Jiaolong Fu (1)

    1. School of Chemistry and Bioengineering, Suzhou University of Science and Technology, Suzhou, 215009, P. R. China
    2. Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin, 300072, P. R. China
  • ISSN:2234-344X
文摘
Tacrolimus (FK506), a 23-membered polyketide macrolide with immunosuppressant activity, can be produced by Streptomyces tsukubaensis. We studied a variety of mutant strains of S. tsukubaensis for the microbial production of FK506. The best strain (CZ-19) was obtained from the parent strain LLZ-1 by nitrosoguanidine mutation and 4-Aminobutyric acid (FK506 precursor structure analogs) adaption. In the shake-flask experiments, titer of FK506 by CZ-19 was 532.44 mg/L, increased by 65.13% compared to that of the parent strain. Through single factor experiments and response surface methodology, we further optimized the medium for improved FK506 production by CZ-19 in shake flask culture. The optimal medium for enhanced FK506 production was as follows: 17.19 g/L corn starch, 21.78 g/L glucose, 8.06 g/L peptone, and 18.98 mg/L 4-aminobutyric acid. The predicted FK506 titer was 906.49 mg/L, and the experimental data confirmed the validity of the model. The present study demonstrates that S. tsukubaensis CZ-19 is a promising strain for industrial production of FK506.

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