FkbN and Tcs7 are pathway-specific regulators of the FK506 biosynthetic gene cluster in Streptomyces tsukubaensis L19

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• 作者：Xiao-Sheng Zhang ; Hong-Dou Luo ; Yang Tao…
• 关键词：FK506 ; Streptomyces tsukubaensis ; Biosynthesis ; Regulatory mechanism
• 刊名：Journal of Industrial Microbiology and Biotechnology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：43
• 期：12
• 页码：1693-1703
• 全文大小：1,981 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Chemistry
  Biotechnology
  Genetic Engineering
  Biochemistry
  Bioinformatics
  Microbiology
  Microbial Genetics and Genomics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1476-5535
• 卷排序：43

文摘

FK506 (tacrolimus), which is produced by many Streptomyces strains, is clinically used as an immunosuppressive agent and for treatment of inflammatory skin diseases. Here, we identified that the FK506 biosynthetic gene cluster in an industrial FK506-producing strain Streptomyces tsukubaensis L19 is organized as eight transcription units. Two pathway-specific regulators, FkbN and Tcs7, involved in FK506 biosynthesis from S. tsukubaensis L19 were characterized in vivo and in vitro. FkbN activates the transcription of six transcription units in FK506 biosynthetic gene cluster, and Tcs7 activates the transcription of fkbN. In addition, the DNA-binding specificity of FkbN was determined. Finally, a high FK506-producing strain was constructed by overexpression of both fkbN and tcs7 in S. tsukubaensis L19, which improved FK506 production by 89 % compared to the parental strain.