Dual regulation between the two-component system PhoRP and AdpA regulates antibiotic production in Streptomyces
Dual regulation between the two-component system PhoRP and AdpA regulates antibiotic production in Streptomyces
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双组分系统 PhoRP 和 AdpA 之间的双重调节调节链霉菌中抗生素的产生
DOI：
10.1007/s10295-018-02127-5
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发表时间：
2019-02
影响因子：
3.4
通讯作者：
Mao Xu Ming
中科院分区：
文献类型：
--
作者：
Zheng Yang;Sun Chen Fan;Fu Yu;Chen Xin Ai;Li Yong Quan;Mao Xu Ming
链霉菌次生代谢过程中抗生素的产生受到多种环境信号和细胞内级联反应的精心控制。其中包括响应磷酸盐饥饿的双组分系统PhoRP和由多效性调节因子AdpA介导的保守信号通路。然而，关于这两种途径如何共同作用于链霉菌次生代谢物产生的信息很少。在此，我们报道了磷酸饥饿响应调节因子PhoP和AdpA对atrA启动子（atrAp）的双重调控，以产生达托霉素（一种由玫瑰孢链霉菌产生的抗生素）。我们发现PhoP直接与atrAp结合，正向调节atrA的表达，从而调节达托霉素的产生。我们还观察到phoRP在产达托霉素的发酵过程中表达的正向自动调节。此外，在atrAp上观察到PhoP-和adpa -结合位点之间的部分重叠，这导致这两个调节因子之间的部分竞争性结合。PhoP和AdpA之间的部分重叠和竞争通过突变和结合实验进一步证实。综上所述，我们的发现揭示了PhoP和AdpA在链霉菌中对同一启动子产生抗生素的双重调控。这一机制将有助于进一步优化抗生素生产的环境响应发酵。
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 confrmed by mutations and binding assays. In summary, our fndings have revealed dual regulation of PhoP and AdpA on the same promoter for antibiotic production in Streptomyces. This mechanism would be benefcial to further environment-responsive fermentation optimization for antibiotic production.
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影响因子：
4.4
作者：
Peng-Hui Yuan;Ri-Cheng Zhou;Xuepeng Chen;Shuai Luo;Feng Wang;X. Mao;Yong-Quan Li
通讯作者：
Peng-Hui Yuan;Ri-Cheng Zhou;Xuepeng Chen;Shuai Luo;Feng Wang;X. Mao;Yong-Quan Li
影响因子：
3.6
作者：
Sola-Landa, A;Rodríguez-García, A;Martín, JF
通讯作者：
Martín, JF
影响因子：
7.7
作者：
Rigali, Sebastien;Titgemeyer, Fritz;van Wezel, Gilles P.
通讯作者：
van Wezel, Gilles P.
DOI：
10.1099/00221287-145-9-2221
发表时间：
1999-09-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Sun, JH;Kelemen, GH;Bibb, MJ
通讯作者：
Bibb, MJ
影响因子：
14.9
作者：
Sola-Landa A;Rodríguez-García A;Amin R;Wohlleben W;Martín JF
通讯作者：
Martín JF