Binding of a biosynthetic intermediate to AtrA modulates the production of lidamycin by Streptomyces globisporus
Binding of a biosynthetic intermediate to AtrA modulates the production of lidamycin by Streptomyces globisporus
复制标题
生物合成中间体与 AtrA 的结合调节球孢链霉菌产生力达霉素
DOI：
10.1111/mmi.13004
复制
发表时间：
2015-06-01
影响因子：
3.6
通讯作者：
Hong, Bin
中科院分区：
文献类型：
--
作者：
Li, Xingxing;Yu, Tengfei;Hong, Bin
链霉菌次级生产的调控涉及到环境和生理信号对生物合成基因的簇定位（转录）调节子（CSR）的调控。对于某些系统，生物合成产物与CSR的结合已显示出提供负反馈。在这里，我们显示了生产力达霉素（C-1027），临床相关的抗肿瘤剂，由链霉菌globisporus，负反馈可以延伸到一个点更高的监管级联。我们表明，DNA结合活性的S.globisporus直向同源物的AtrA，这最初被描述为一个转录激活剂的放线菌紫素生物合成的天蓝色链霉菌，被抑制的heptaene，力达霉素的生物合成中间体的结合。本文所述的其他实验表明，球孢链霉菌AtrA在体内和体外均与编码SgcR 1的基因的启动子区结合，SgcR 1是力达霉素生产的CSR之一。多效性调节剂AtrA的反馈可能提供一种机制，用于协调力达霉素与其他次级代谢产物的生产。AtrA的活性也受到放线菌紫素的调节。由于AtrA在进化上是保守的，这里描述的负反馈类型可能在链霉菌中广泛存在。
The control of secondary production in streptomycetes involves the funneling of environmental and physiological signals to the cluster-situated (transcriptional) regulators (CSRs) of the biosynthetic genes. For some systems, the binding of biosynthetic products to the CSR has been shown to provide negative feedback. Here we show for the production of lidamycin (C-1027), a clinically relevant antitumor agent, by Streptomyces globisporus that negative feedback can extend to a point higher in the regulatory cascade. We show that the DNA-binding activity of the S.globisporus orthologue of AtrA, which was initially described as a transcriptional activator of actinorhodin biosynthesis in S.coelicolor, is inhibited by the binding of heptaene, a biosynthetic intermediate of lidamycin. Additional experiments described here show that S.globisporusAtrA binds in vivo as well as in vitro to the promoter region of the gene encoding SgcR1, one of the CSRs of lidamycin production. The feedback to the pleiotropic regulator AtrA is likely to provide a mechanism for coordinating the production of lidamycin with that of other secondary metabolites. The activity of AtrA is also regulated by actinorhodin. As AtrA is evolutionarily conserved, negative feedback of the type described here may be widespread within the streptomycetes.