Positive and negative regulation of GlnR in validamycin A biosynthesis by binding to different loci in promoter region
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- 作者：Shuang Qu ; Qianjin Kang ; Hang Wu ; Lei Wang…
- 关键词：Streptomyces ; GlnR ; Validamycin ; Regulation ; Antibiotics
- 刊名：Applied Microbiology and Biotechnology
- 出版年：2015
- 出版时间：June 2015
- 年：2015
- 卷：99
- 期：11
- 页码：4771-4783
- 全文大小：1,298 KB
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Qianjin Kang (1) (2)
Hang Wu (1) (3)
Lei Wang (1) (2)
Linquan Bai (1) (2)
1. State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
2. Joint International Research Laboratory of Metabolic and Developmental Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China
3. School of Life Sciences, Anhui University, Hefei, 230601, China - 刊物类别：Chemistry and Materials Science
- 刊物主题：Chemistry
Biotechnology
Microbiology
Microbial Genetics and Genomics - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-0614
文摘
Validamycin A (VAL-A) is a C7N aminocyclitol antibiotic produced by Streptomyces hygroscopicus var. jinggangensis 5008, which has been widely used as antifungal agent against rice sheath blight disease. VAL-A biosynthesis has been proven to be affected by γ-butyrolactone and temperature. Herein, we showed that GlnR, a global regulator in nitrogen metabolism, is specifically associated with valK-valA intergenic promoter region by DNA-affinity chromatography and MS-based protein identification. Subsequent EMSA and DNase I footprinting assays revealed two GlnR binding sites in this promoter region. Targeted disruption of glnR in S. hygroscopicus 5008 led to a significant increase in the transcription of VAL-A structural genes, albeit the VAL-A production was reduced by 80?% and the sporulation of the mutant was impaired. Compared with the wild-type 5008, site-specific mutagenesis of GlnR binding site I enhanced VAL-A production by 2.5-fold, whereas the mutation of GlnR binding site II resulted in a 50?% reduction of VAL-A yield. Moreover, tandem mutation of site I in the site II mutant led to a 66?% increase of VAL-A production. The result suggested that GlnR not only serves as an inhibitor by binding site I but also as an activator by binding site II for VAL-A biosynthesis. Furthermore, overexpression of glnR in the site I mutant JG45 improved VAL-A production for 41?% compared with the control strain containing the vector. Therefore, the obtained data illustrate a novel regulatory feature of the global regulator GlnR. GlnR is firstly proved to act simultaneously as an activator and a repressor in validamycin biosynthesis by binding to different loci within a promoter region of the gene cluster.