Deletion of a regulatory gene within the cpk gene cluster reveals novel antibacterial activity in Streptomyces coelicolor A3(2)

Deletion of a regulatory gene within the cpk gene cluster reveals novel antibacterial activity in Streptomyces coelicolor A3(2)
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DOI:
10.1099/mic.0.038281-0
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发表时间:
2010-08-01
期刊:
影响因子:
2.8
通讯作者:
Takano, Eriko
Takano, Eriko
中科院分区:
生物学4区
文献类型:
--
作者:
Gottelt, Marco;Kol, Stefan;Takano, Eriko

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天蓝色链霉菌A3(2)的基因组测序揭示了一个未知的I型聚酮合成酶基因簇(CPK)。在这里,我们描述了一个新的抗菌活性(AbCPK)和一个黄色素次生代谢物(YCPK)的发现。在scbR2缺失突变体中过量生产yCPK和abCPK,以及在CPK缺失突变体中没有新描述的化合物,这表明它们是先前孤立的CPK生物合成途径的产物,在该途径中abCPK被转化为黄色素。转录分析表明,scbR2可能发挥负反馈机制,最终限制yCPK的生物合成。这里描述的结果为发现新的生物活性化合物提供了一种新的方法。
Genome sequencing of Streptomyces coelicolor A3(2) revealed an uncharacterized type I polyketide synthase gene cluster (cpk) Here we describe the discovery of a novel antibacterial activity (abCPK) and a yellow-pigmented secondary metabolite (yCPK) after deleting a presumed pathway-specific regulatory gene (scbR2) that encodes a member of the gamma-butyrolactone receptor family of proteins and which lies in the cpk gene cluster. Overproduction of yCPK and abCPK in a scbR2 deletion mutant, and the absence of the newly described compounds from cpk deletion mutants, suggest that they are products of the previously orphan cpk biosynthetic pathway in which abCPK is converted into the yellow pigment. Transcriptional analysis suggests that scbR2 may act in a negative feedback mechanism to eventually limit yCPK biosynthesis The results described here represent a novel approach for the discovery of new, biologically active compounds.