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SlnR is a positive pathway-specific regulator for salinomycin biosynthesis in Streptomyces albus

  • Applied genetics and molecular biotechnology
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Abstract

Salinomycin, a polyether antibiotic produced by Streptomyces albus, is widely used in animal husbandry as an anticoccidial drug and growth promoter. Situated within the salinomycin biosynthetic gene cluster, slnR encodes a LAL-family transcriptional regulator. The role of slnR in salinomycin production in S. albus was investigated by gene deletion, complementation, and overexpression. Gene replacement of slnR from S. albus chromosome results in almost loss of salinomycin production. Complementation of slnR restored salinomycin production, suggesting that SlnR is a positive regulator of salinomycin biosynthesis. Overexpression of slnR in S. albus led to about 25 % increase in salinomycin production compared to wild type. Quantitative RT-PCR analysis revealed that the expression of most sal structural genes was downregulated in the ΔslnR mutant but upregulated in the slnR overexpression strain. Electrophoretic mobility gel shift assays (EMSAs) also revealed that SlnRDBD binds directly to the three intergenic regions of slnQ-slnA1, slnF-slnT1, and slnC-slnB3. The SlnR binding sites within the three intergenic regions were determined by footprinting analysis and identified a consensus-directed repeat sequence 5′-ACCCCT-3′. These results indicated that SlnR modulated salinomycin biosynthesis as an enhancer via interaction with the promoters of slnA1, slnQ, slnF, slnT1, slnC, and slnB3 and activates the transcription of most of the genes belonging to the salinomycin gene cluster but not its own transcription.

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Acknowledgments

This study was supported by the National Basic Research Program of China (No. 2012CB721005), National High Technology Research and Development Program of China (No. 2012AA022107), and Zhejiang Provincial Natural Science Foundation of China (Nos. LY16C010001, LZ12C01001).

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Authors and Affiliations

  1. College of pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

    Zhenhong Zhu, Han Li, Pin Yu, Yuanyang Guo, Shuai Luo, Xuming Mao, Wenjun Guan & Yongquan Li

  2. College of Life Sciences, Zhejiang University, Hangzhou, 310058, China

    Zhenhong Zhu, Han Li, Pin Yu, Yuanyang Guo & Shuai Luo

  3. College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China

    Zhenhong Zhu

  4. Zhejiang ShenghuaBiok Biology Co., Ltd, Zhongguan Industrial Park, Zhejiang, Deqing, 312110, China

    Zhongbin Chen

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  1. Zhenhong Zhu
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  2. Han Li
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  3. Pin Yu
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Correspondence to Yongquan Li.

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Zhu, Z., Li, H., Yu, P. et al. SlnR is a positive pathway-specific regulator for salinomycin biosynthesis in Streptomyces albus . Appl Microbiol Biotechnol 101, 1547–1557 (2017). https://doi.org/10.1007/s00253-016-7918-5

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