新多环特特拉姆酸大环内酰胺3-HydroxycombamideⅠ的发现

Discovery of a New Polycyclic Tetramate Macrolactam 3-Hydroxycombamide Ⅰ

从链霉菌S001的重组菌株S001-cbm-OX4-ikaD中分离获得1个新多环特特拉姆酸大环内酰胺(Po TeMs)类化合物3-hydroxycombamide Ⅰ (2),通过一维、二维核磁共振波谱(NMR)和高分辨质谱(HRMS)数据分析确定其化学结构.化合物2的C-3位羟基推测为宿主链霉菌S001所含羟基化酶催化形成.分别采用滤纸片法和噻唑蓝(MTT)比色法测定了化合物2的抗菌和细胞毒活性,结果显示化合物2无明显活性.此外,化合物2在100μmol/L时对鼠伤寒沙门菌Ⅲ型分泌系统(T3SS)无抑制活性.结果显示Po TeMs的C-3位羟基化修饰可能发生在多环体系氧化修饰之后.

3-Hydroxycombamide Ⅰ(2), a new polycyclic tetramate macrolactam(PoTeM) bearing a 5/5/6 cyclization pattern was isolated from the recombinant strain S001-cbm-OX4-ikaD, which is derived from Streptomyces sp. S001 by integration of the modified combamides biosynthetic gene cluster. The chemical structure of 2 was determined by analysis of 1D and 2D-NMR and HRMS data. The hydroxylation of compound 2 at C-3 was deduced to be catalyzed by a hydroxylase of Streptomyces sp. S001. The antibacterial and cytotoxic activity of compound 2 was evaluated by filter paper disc diffusion and methyl thiazolyl tetrazolium(MTT) assay, respectively. The effect of compound 2 on inhibition of the T3SS(type Ⅲ secretion system) of Salmonella enterica serovar Typhimurium was also investigated. However, compound 2 was inactivity in all assays.The results indicated that the hydroxylation at C-3 may occurs after the oxidative modifictions of the polycyclic system in the biosynthesis of PoTeMs.