Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Kerklaan 30, 9751NN Haren, The Netherlands.
Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK.
Microbiology (Reading). 2010 Aug;156(Pt 8):2343-2353. doi: 10.1099/mic.0.038281-0. Epub 2010 May 6.
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.
链霉菌 A3(2) 的基因组测序揭示了一个未被描述的 I 型聚酮合酶基因簇 (cpk)。在这里，我们描述了在删除一个假定的途径特异性调节基因 (scbR2) 后，发现了一种新的抗菌活性 (abCPK) 和一种黄色色素次生代谢物 (yCPK)，该基因编码一种γ-丁内酯受体家族的蛋白质成员，位于 cpk 基因簇中。在 scbR2 缺失突变体中过表达 yCPK 和 abCPK，以及在 cpk 缺失突变体中没有新描述的化合物，表明它们是以前孤儿 cpk 生物合成途径的产物，其中 abCPK 转化为黄色色素。转录分析表明，scbR2 可能在负反馈机制中起作用，最终限制 yCPK 的生物合成。这里描述的结果代表了一种发现新的、具有生物活性的化合物的新方法。
