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DasR positively controls monensin production at two-level regulation in Streptomyces cinnamonensis

  • Genetics and Molecular Biology of Industrial Organisms - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

The polyether ionophore antibiotic monensin is produced by Streptomyces cinnamonensis and is used as a coccidiostat for chickens and growth-promoting agent for cattle. Monensin biosynthetic gene cluster has been cloned and partially characterized. The GntR-family transcription factor DasR regulates antibiotic production and morphological development in Streptomyces coelicolor and Saccharopolyspora erythraea. In this study, we identified and characterized the two-level regulatory cascade of DasR to monensin production in S. cinnamonensis. Forward and reverse genetics by overexpression and antisense RNA silence of dasR revealed that DasR positively controls monensin production under nutrient-rich condition. Electrophoresis mobility shift assay (EMSA) showed that DasR protein specifically binds to the promoter regions of both pathway-specific regulatory gene monRII and biosynthetic genes monAIX, monE and monT. Semi-quantitative RT-PCR further confirmed that DasR upregulates the transcriptional levels of these genes during monensin fermentation. Subsequently, co-overexpressed dasR with pathway-specific regulatory genes monRI, monRII or monH greatly improved monensin production.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (31370092) and the National Basic Research Program of China (2012CB721105).

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Authors and Affiliations

  1. Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin, 300072, China

    Yue Zhang, Chun-Yan Lin, Xiao-Mei Li, Zheng-Kun Tang, Jianjun Qiao & Guang-Rong Zhao

  2. Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, University, Tianjin, 300072, China

    Yue Zhang, Chun-Yan Lin, Xiao-Mei Li, Zheng-Kun Tang, Jianjun Qiao & Guang-Rong Zhao

  3. SynBio Research Platform, Collaborative, Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, 300072, China

    Yue Zhang, Chun-Yan Lin, Xiao-Mei Li, Zheng-Kun Tang, Jianjun Qiao & Guang-Rong Zhao

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  1. Yue Zhang
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Correspondence to Guang-Rong Zhao.

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Zhang, Y., Lin, CY., Li, XM. et al. DasR positively controls monensin production at two-level regulation in Streptomyces cinnamonensis . J Ind Microbiol Biotechnol 43, 1681–1692 (2016). https://doi.org/10.1007/s10295-016-1845-4

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