Dual regulation between the two-component system PhoRP and AdpA regulates antibiotic production in Streptomyces
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Antibiotic production during secondary metabolism in Streptomyces spp. is elaborately controlled by multiple environmental signals and intracellular cascades. These include the two-component system PhoRP responding to phosphate starvation and a conserved signaling pathway mediated by the pleiotropic regulator AdpA. However, little information exists about how these two pathways work together for secondary metabolite production of Streptomyces. Herein, we report the dual regulation from the phosphate starvation-responsive regulator PhoP and AdpA on atrA promoter (atrAp) for the production of daptomycin, an antibiotic produced by Streptomyces roseosporus. We found that PhoP directly binds to atrAp, positively regulates atrA expression and thus daptomycin production. We also observed positive auto-regulation of phoRP expression during fermentation for daptomycin production. Moreover, partial overlap between PhoP- and AdpA-binding sites on atrAp was observed, which results in partial competitive binding between these two regulators. This partial overlapping and competition between PhoP and AdpA was further confirmed by mutations and binding assays. In summary, our findings have revealed dual regulation of PhoP and AdpA on the same promoter for antibiotic production in Streptomyces. This mechanism would be beneficial to further environment-responsive fermentation optimization for antibiotic production.
KeywordsStreptomyces Secondary metabolism Dual transcriptional regulation Antibiotic production PhoP AdpA
This work was financially supported by National Natural Science Foundation of China (3173002, 31520103901, 31470212) to Yong-Quan Li and (31571284) to Xu-Ming Mao.
X-MM, Y-QL, and X-AC conceived and designed the experiments. YZ, C-FS, and YF performed the experiments. All the authors analyzed the data. YZ, X-MM, and Y-QL wrote and edited the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare no competing financial interests.
Compliance with ethics requirements
This article does not contain any studies with human or animal subjects performed by any of the authors.
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