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Clarification of mechanism for antibiotic production regulated by Streptomyces signaling molecules.

阐明链霉菌信号分子调节抗生素生产的机制。

基本信息

批准号：
15380063
负责人：
NIHIRA Takuya
金额：
$ 10.11万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Streptomyces species are gram-positive soil-dwelling filamentous bacteria that produce a wide variety of antibiotic and other secondary metabolites with important applications in human medicine and agriculture. These secondary metabolites are products of complex biosynthetic pathways including regulatory genes as well as their biosynthetic gene cluster. The activation of antibiotic production has been known to be controlled by the γ-butyrolactone autoregulator, a low-molecular-weight signaling molecule. Although the autoregulator-mediated mechanism has been partially clarified in many Streptomyces species, common trait has still remained unclear. In this research, we focused on framework for autoregulator-mediated mechanism by assembling information from each analysis. In Streptomyces virginiae, the autoregulator (VB) controls virginiamycin production by means of VB binding to VB receptor (BarA). Our analysis on BarB and BarZ, which possess moderate similarity to BarA, showed that virginiamycin production requires function of BarB and BarZ at initial or stationary phase, respectively. barB transcription is directly controlled by BarA binding to barB promoter region. In S.coelicolor A3(2), the model strain of Streptomyces species, autoregulator receptor was found to regulate directly transcriptional regulator, and thus controls expression of biosynthetic genes concerned with secondary metabolism. Moreover, we obtained 4 more autoregulator receptors from industrially important Streptomyces and non-Streptomyces strains. Taken together with these results, we conclude that useful information was successfully accumulated for industrial application.

链霉菌属是革兰氏阳性的土壤丝状细菌，其产生多种抗生素和其他次级代谢产物，在人类医学和农业中具有重要应用。这些次级代谢产物是包括调控基因及其生物合成基因簇在内的复杂生物合成途径的产物。已知抗生素生产的激活由γ-丁内酯自动调节因子（一种低分子量信号分子）控制。虽然自调节因子介导的机制在许多链霉菌中已部分阐明，但共同的性状仍不清楚。在这项研究中，我们集中在框架自动调节介导的机制，通过收集信息，从每个分析。在维吉尼亚链霉菌中，自动调节因子（VB）通过与VB受体（BarA）结合来控制维吉尼亚霉素的产生。我们对BarB和BarZ（与BarA具有中等相似性）的分析表明，维吉尼亚霉素的生产分别需要BarB和BarZ在初始或稳定期起作用。barB的转录直接受BarA与barB启动子区结合的调控。在链霉菌模式菌株天蓝色链霉菌A3（2）中，发现自身调节因子受体直接调控转录调节因子，从而调控与次生代谢相关的生物合成基因的表达。此外，我们还从工业上重要的链霉菌和非链霉菌菌株中获得了4种以上的自调节受体。结合这些结果，我们得出结论，有用的信息，成功地积累了工业应用。

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The SCB1 signalling system directly controls an antibiotic pathway-specific regulator in the cryptic type I polyketide biosynthetic cluster of Streptomyces coelicolor A3(2)

SCB1 信号系统直接控制天蓝色链霉菌 A3(2) 隐秘的 I 型聚酮化合物生物合成簇中的抗生素途径特异性调节因子

DOI：
发表时间：
2005
期刊：
Mol.Microbiol. (In press)
影响因子：
0
作者：
Takano;E.;Konoshita;H.;Mersinias;V.;Bucca;G.;Hotchkiss;G.;Nihira;T.;Smith;C.;Bibb;M.;Wohleben;W.;Chater;K.
通讯作者：
K.

Cloning and characterization of a gene encoding the γ-butyrolactone autoregulator receptor from Saccharopolyspora erythrae.

红斑糖多孢菌编码 γ-丁内酯自动调节受体的基因的克隆和表征。