Genome Mining of Marine-Derived Streptomyces sp. SCSIO 40010 Leads to Cytotoxic New Polycyclic Tetramate Macrolactams
Genome Mining of Marine-Derived Streptomyces sp. SCSIO 40010 Leads to Cytotoxic New Polycyclic Tetramate Macrolactams
复制标题
海洋来源的链霉菌基因组挖掘。
DOI：
10.3390/md17120663
复制
发表时间：
2019-12-01
期刊：
影响因子：
5.4
通讯作者：
Zhang, Changsheng
中科院分区：
文献类型：
--
作者：
Liu, Wei;Zhang, Wenjun;Zhang, Changsheng
多环四酸酯大内酰胺（PTM）生物合成基因簇广泛分布于不同细菌类型中，尤其是链霉菌属物种中。海洋来源的链霉菌基因组数据的挖掘。 SCSIO 40010 揭示了假定的 PTM 编码生物合成基因簇 (ptm' BGC) 的存在，其特征是可能产生 5/5/6 型含碳环 PTM 的遗传组织。链霉菌发酵。 SCSIO 40010 导致了六个新 PTM 1-6 的分离和表征。综合光谱分析确定了它们的平面结构和相对构型，并通过将实验电子圆二色性 (ECD) 光谱与已知 PTM 的报告光谱进行比较，推导出它们的绝对构型。有趣的是，化合物 1-6 被确定在第一个 5 元环处具有 H-10/H-11 的反式取向，这与它们已知的 PTM 同系物中的顺式取向不同。 PTM 1-5 对多种癌细胞系表现出细胞毒性，IC50 值范围为 2.47 至 17.68 muM。
Polycyclic tetramate macrolactams (PTMs) biosynthetic gene cluster are widely distributed in different bacterial types, especially in Streptomyces species. The mining of the genomic data of marine-derived Streptomyces sp. SCSIO 40010 reveals the presence of a putative PTM-encoding biosynthetic gene cluster (ptm ' BGC) that features a genetic organization for potentially producing 5/5/6 type of carbocyclic ring-containing PTMs. A fermentation of Streptomyces sp. SCSIO 40010 led to the isolation and characterization of six new PTMs 1-6. Comprehensive spectroscopic analysis assigned their planar structures and relative configurations, and their absolute configurations were deduced by comparing the experimental electronic circular dichroism (ECD) spectra with the reported spectra of the known PTMs. Intriguingly, compounds 1-6 were determined to have a trans-orientation of H-10/H-11 at the first 5-membered ring, being distinct from the cis-orientation in their known PTM congeners. PTMs 1-5 displayed cytotoxicity against several cancer cell lines, with IC50 values that ranged from 2.47 to 17.68 mu M.