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.

当在谷氨酸下生长时，双组分系统“AfsQ1/Q2”通过直接结合通路特异性激活基因actII-ORF4、redZ和cdaR的启动子，对激活抗生素 ACT、RED 和 CDA 的产生起着至关重要的作用-天蓝色链霉菌中补充的基本培养基。在本报告中，我们证明了 RspA1/A2（双组分系统 AfsQ1/Q2 的同源蛋白）在白化链霉菌中的盐霉素生物合成中发挥调节作用。. 基因缺失和互补实验表明，在补充有 3% 大豆油的 YMG 培养基中培养时，RspA1/A2 促进了盐霉素的产生，但抑制了细胞生长。更重要的是，RspA1/A2 通过直接影响通路特异性激活基因slnR的转录来增强盐霉素的生物合成。同时，RspA1/A2 通过与基因gdhA、glnA、amtB和SLNWT_1828/1829的启动子相互作用，在氮同化和尿素脱羧的调节中起负面作用。基因sigW位于rspA1/A2 的下游并编码胞质外功能σ因子。此外，它负向调节盐霉素生物合成并促进细胞生长，从而拮抗 RspA1/A2 的功能。简而言之，这些有用的发现被证明有助于丰富对链霉菌中ECF σ 因子-TCS 信号转导系统抗生素生物合成调控途径的理解。