Huang Jianqiang, Shi Jing, Molle Virginie, Sohlberg Björn, Weaver David, Bibb Maureen J, Karoonuthaisiri Nitsara, Lih Chih-Jian, Kao Camilla M, Buttner Mark J, Cohen Stanley N
Department of Genetics, MC 5120, Stanford University, Stanford, CA 94305, USA.
Mol Microbiol. 2005 Dec;58(5):1276-87. doi: 10.1111/j.1365-2958.2005.04879.x.
A complex programme of regulation governs gene expression during development of the morphologically and biochemically complex eubacterial genus Streptomyces. Earlier work has suggested a model in which 'higher level' pleiotropic regulators activate 'pathway-specific' regulators located within chromosomal gene clusters encoding biosynthesis of individual antibiotics. We used mutational analysis and adventitious overexpression of key Streptomyces coelicolor regulators to investigate functional interactions among them. We report here that cluster-situated regulators (CSRs) thought to be pathway-specific can also control other antibiotic biosynthetic gene clusters, and thus have pleiotropic actions. Surprisingly, we also find that CSRs exhibit growth-phase-dependent control over afsR2/afsS, a 'higher level' pleiotropic regulatory locus not located within any of the chromosomal gene clusters it targets, and further demonstrate that cross-regulation by CSRs is modulated globally and differentially during the S. coelicolor growth cycle by the RNaseIII homologue AbsB. Our results, which reveal a network of functional interactions among regulators that govern production of antibiotics and other secondary metabolites in S. coelicolor, suggest that revision of the currently prevalent view of higher-level versus pathway-specific regulation of secondary metabolism in Streptomyces species is warranted.
在形态学和生物化学上都很复杂的真细菌属链霉菌的发育过程中，一个复杂的调控程序控制着基因表达。早期的研究提出了一个模型，即“更高级别的”多效性调节因子激活位于编码单个抗生素生物合成的染色体基因簇内的“途径特异性”调节因子。我们利用突变分析和天蓝色链霉菌关键调节因子的偶然过表达来研究它们之间的功能相互作用。我们在此报告，被认为是途径特异性的簇状调节因子（CSRs）也可以控制其他抗生素生物合成基因簇，因此具有多效性作用。令人惊讶的是，我们还发现CSRs对afsR2/afsS表现出依赖生长阶段的控制，afsR2/afsS是一个“更高级别的”多效性调节位点，它并不位于其靶向的任何染色体基因簇内，并且进一步证明，在天蓝色链霉菌生长周期中，CSRs的交叉调节受到核糖核酸酶III同源物AbsB的全局和差异调节。我们的结果揭示了天蓝色链霉菌中控制抗生素和其他次级代谢产物产生的调节因子之间的功能相互作用网络，这表明有必要修正目前关于链霉菌物种次级代谢中更高级别与途径特异性调节的普遍观点。
