Role of sgcR3 in positive regulation of enediyne antibiotic C-1027 production of Streptomyces globisporus C-1027.
Role of sgcR3 in positive regulation of enediyne antibiotic C-1027 production of Streptomyces globisporus C-1027.
复制标题
sgcR3 在球孢链霉菌 C-1027 烯二炔抗生素 C-1027 生产中的正调控作用
DOI：
10.1186/1471-2180-9-14
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发表时间：
2009-01-22
期刊：
影响因子：
4.2
通讯作者：
Hong B
中科院分区：
文献类型：
--
作者：
Wang L;Hu Y;Zhang Y;Wang S;Cui Z;Bao Y;Jiang W;Hong B
背景
C-1027是由球孢链霉菌C-1027产生的一种抗肿瘤活性物质。先前克隆和测序的C-1027的生物合成基因簇包含至少三个推定的调控基因，即sgcR 1、sgcR 2和sgcR 3。这些基因的预测基因产物与StrR、AraC/XylS家族的调节子和TylR具有序列相似性。本研究的目的是研究sgcR 3在C-1027生物合成中的作用。
结果
sgcR 3在S. globisporus C-1027导致C-1027产量增加30-40%。与此一致，sgcR 3的破坏消除了C-1027的产生。用完整的sgcR 3基因互补sgcR 3破坏的菌株R3 KO可以恢复C-1027的生产。对R3 KO突变株和野生型菌株的真实的实时RT-PCR分析结果表明，R3 KO突变株不仅生物合成结构基因sgcA 1和sgcC 4的转录水平明显降低，而且推测的调控基因sgcR 1和sgcR 2的转录水平也明显降低。交叉互补研究表明，sgcR 1 R2可以在功能上互补sgcR 3的破坏反式。纯化的N-末端His 10标记的SgcR 3显示出特异性的DNA结合活性的启动子区的sgcR 1 R2。
结论
SgcR 3在S. globisporus C-1027。SgcR 3在控制C-1027产生的调控层级中占据比SgcR 1和SgcR 2更高的水平，并通过直接结合sgcR 1 R2的启动子区来激活sgcR 1和sgcR 2的转录。
Background
C-1027, produced by Streptomyces globisporus C-1027, is one of the most potent antitumoral agents. The biosynthetic gene cluster of C-1027, previously cloned and sequenced, contains at least three putative regulatory genes, i.e. sgcR1, sgcR2 and sgcR3. The predicted gene products of these genes share sequence similarities to StrR, regulators of AraC/XylS family and TylR. The purpose of this study was to investigate the role of sgcR3 in C-1027 biosynthesis.
Results
Overexpression of sgcR3 in S. globisporus C-1027 resulted in a 30–40% increase in C-1027 production. Consistent with this, disruption of sgcR3 abolished C-1027 production. Complementation of the sgcR3-disrupted strain R3KO with intact sgcR3 gene could restore C-1027 production. The results from real time RT-PCR analysis in R3KO mutant and wild type strain indicated that not only transcripts of biosynthetic structural genes such as sgcA1 and sgcC4, but also putative regulatory genes, sgcR1 and sgcR2, were significantly decreased in R3KO mutant. The cross-complementation studies showed that sgcR1R2 could functionally complement sgcR3 disruption in trans. Purified N-terminal His10-tagged SgcR3 showed specific DNA-binding activity to the promoter region of sgcR1R2.
Conclusion
The role of SgcR3 has been proved to be a positive regulator of C-1027 biosynthesis in S. globisporus C-1027. SgcR3 occupies a higher level than SgcR1 and SgcR2 in the regulatory hierarchy that controls C-1027 production and activates the transcription of sgcR1 and sgcR2 by binding directly to the promoter region of sgcR1R2.
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影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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