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The PhoP transcription factor negatively regulates avermectin biosynthesis in Streptomyces avermitilis

  • Applied genetics and molecular biotechnology
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Abstract

Bacteria sense and respond to the stress of phosphate limitation, anticipating Pi deletion/starvation via the two-component PhoR–PhoP system. The role of the response regulator PhoP in primary metabolism and avermectin biosynthesis in Streptomyces avermitilis was investigated. In response to phosphate starvation, S. avermitilis PhoP, like Streptomyces coelicolor and Streptomyces lividans PhoP, activates the expression of phoRP, phoU, and pstS by binding to the PHO boxes in their promoter regions. Avermectin biosynthesis was significantly increased in ΔphoP deletion mutants. Electrophoretic mobility gel shift assay (EMSA) and DNase I footprinting assays showed that PhoP can bind to a PHO box formed by two direct repeat units of 11 nucleotides located downstream of the transcriptional start site of aveR. By negatively regulating the transcription of aveR, PhoP directly affects avermectin biosynthesis in S. avermitilis. PhoP indirectly affects melanogenesis on Casaminoacids Minimal Medium (MMC) lacking supplemental phosphate. Nitrogen metabolism and some key genes involved in morphological differentiation and antibiotic production in S. avermitilis are also under the control of PhoP.

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Acknowledgments

This work was supported by grants from the National Science Foundation of China (Grant Nos. 31170090 and 31470190).

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This study was funded by the National Science Foundation of China (Grant Nos. 31170090 and 31470190).

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Correspondence to Zhi Chen.

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Yang, R., Liu, X., Wen, Y. et al. The PhoP transcription factor negatively regulates avermectin biosynthesis in Streptomyces avermitilis . Appl Microbiol Biotechnol 99, 10547–10557 (2015). https://doi.org/10.1007/s00253-015-6921-6

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