Role of a Two-Component Signal Transduction System RspA1/A2 in Regulating the Biosynthesis of Salinomycin in Streptomyces albus


The two-component system “AfsQ1/Q2” plays a crucial role to activate the production of antibiotics ACT, RED, and CDA through directly binding the promoters of pathway-specific activator genes actII-ORF4, redZ, and cdaR respectively when grown under glutamate-supplemented minimal medium in Streptomyces coelicolor. In this report, we demonstrated that the RspA1/A2 (a homologous protein of two-component system AfsQ1/Q2) plays a regulatory role in salinomycin biosynthesis in Streptomyces albus. Gene deletion and complementation experiments showed that the RspA1/A2 promoted salinomycin production but inhibited cell growth when cultured in YMG medium supplemented with 3% soybean oil. More importantly, RspA1/A2 strengthens salinomycin biosynthesis by directly affecting the transcription of the pathway-specific activator gene slnR. Meanwhile, RspA1/A2 plays a negative role in the regulation of nitrogen assimilation and urea decarboxylation by interacting with the promoters of genes gdhA, glnA, amtB, and SLNWT_1828/1829. Gene sigW is located downstream of rspA1/A2 and encodes an extracytoplasmic function sigma factor. Moreover, it negatively regulates the salinomycin biosynthesis and promotes cell growth, which antagonizes the function of RspA1/A2. In short, these useful findings are proved helpful to enrich the understanding of the regulatory pathways of antibiotic biosynthesis by an ECF σ factor-TCS signal transduction system in Streptomyces.

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We thank Zhejiang Biok Biology Co., Ltd. for providing strains and other experimental help.


This research was supported by the National Natural Science Foundation of China (81373286) and Fundamental Research Funds for the China Central Universities (No.22221818014 and No.22221817014) and 111 Project (B18022) to Meijin Guo.

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All authors saw and approved the manuscript. All authors contributed significantly to the work. Meijin Guo and Kuipu Zhang conceived the project. Meijin Guo, Kuipu Zhang designed experiments and analyzed results. Kuipu Zhang wrote the manuscript with the help of Ali Mohsin, Muhammad Fahad Ali, Meijin Guo, Yingping Zhuang, and Ju Chu. Kuipu Zhang performed experiments, supported by Yichen Dai, Zhongbing Chen.

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Correspondence to Meijin Guo.

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Author Zhongbing Chen was employed by the company Zhejiang Biok Biology Co., Ltd. All other authors declare no competing interests.

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The presenting author of this manuscript in ACB2019 is Kuipu Zhang.

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Zhang, K., Mohsin, A., Dai, Y. et al. Role of a Two-Component Signal Transduction System RspA1/A2 in Regulating the Biosynthesis of Salinomycin in Streptomyces albus. Appl Biochem Biotechnol 193, 1296–1310 (2021).

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  • Streptomyces albus
  • Salinomycin biosynthesis
  • Regulation
  • Two-component system
  • Urea decarboxylation