Positive Feedback Regulation of stgR Expression for Secondary Metabolism in Streptomyces coelicolor
Positive Feedback Regulation of stgR Expression for Secondary Metabolism in Streptomyces coelicolor
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天蓝色链霉菌次生代谢stgR表达的正反馈调节
DOI：
10.1128/jb.00040-13
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发表时间：
2013-05-01
影响因子：
3.2
通讯作者：
Li, Yong-Quan
中科院分区：
文献类型：
--
作者：
Mao, Xu-Ming;Sun, Zhi-Hao;Li, Yong-Quan
LysR型转录调节因子（LTTR）组成一个大家族，负责细菌的多种生理功能，但其对链霉菌次生代谢的调节机制知之甚少。在这里，我们报道了StgR，天蓝色链霉菌中的典型LTTR，通过分别抑制两个途径特异性调节基因redD和actII-orf4的表达，在次生代谢的早期发育阶段对十一烷基灵菌红素（Red）和γ-放线菌素（Act）产生负调节。同时，stgR 表达在次级代谢过程中下调，以消除其对抗生素产生的抑制作用。此外，stgR 的表达通过 StgR 与其自身启动子 (stgRp) 的直接结合而受到正向自动调节，并且通过 DNase I 足迹分析确定了与翻译起始密码子相邻的结合位点。此外，StgR-stgRp 相互作用可以被天蓝色链球菌产生的抗生素γ-放线菌素破坏。因此，我们的结果表明stgR表达和抗生素产生的正反馈调节机制促进了链霉菌次生代谢的快速和不可逆的发展。
LysR-type transcriptional regulators (LTTRs) compose a large family and are responsible for various physiological functions in bacteria, while little is understood about their regulatory mechanism on secondary metabolism in Streptomyces. Here we reported that StgR, a typical LTTR in Streptomyces coelicolor, was a negative regulator of undecylprodigiosin (Red) and gamma-actinorhodin (Act) production in the early developmental phase of secondary metabolism by suppressing the expression of two pathway-specific regulator genes, redD and actII-orf4, respectively. Meanwhile, stgR expression was downregulated during secondary metabolism to remove its repressive effects on antibiotic production. Moreover, stgR expression was positively autoregulated by direct binding of StgR to its own promoter (stgRp), and the binding site adjacent to translation start codon was determined by a DNase I footprinting assay. Furthermore, the StgR-stgRp interaction could be destroyed by the antibiotic gamma-actinorhodin produced from S. coelicolor. Thus, our results suggested a positive feedback regulatory mechanism of stgR expression and antibiotic production for the rapid and irreversible development of secondary metabolism in Streptomyces.