链霉菌S001代谢产生的多环特特拉姆酸大环内酰胺

New Polycyclic Tetramate Macrolactam from Streptomyces sp.S001

从链霉菌S001的重组菌株S001-PoTeM(S023)中分离获得1个结构新颖的含有5/5/6三环体系的多环特特拉姆酸大环内酰胺(PoTeMs)类化合物montamide A (1),通过一维和二维核磁(NMR)、高分辨质谱和圆二色谱确定了其化学结构.采用滤纸片法测定了化合物1的抗细菌和抗真菌活性,结果显示在载样量40μg时化合物1无抗菌活性;采用噻唑蓝(MTT)比色法测定了化合物1的细胞毒活性,结果显示化合物1对人肺癌细胞A549有较弱的细胞毒性(IC(50)~22.6μmol/L),其中C16位为细胞毒活性关键位点.此外,在链霉菌S001基因组中定位了化合物1的生物合成基因簇mtm,推测了其可能的生物合成途径.

Montamide A(1),a new polycyclic tetramate macrolactam(PoTeM)with a 5/5/6 tricyclic system was isolated from recombinant strain S001-PoTeMS023,which is derived from Streptomyces sp.S001 by introducing a new PoTeM biosynthetic gene cluster cftS023.The chemical structure of 1 was elucidated by different spectroscopic techniques including HRMS,1D and 2D-NMR and ECD spectroscopies.The antibacterial and antifungal activities of compound 1 were carried out by filter paper disc diffusion assay.The results showed that compound 1 has no effect on tested strains at 40μg/disc.The cytotoxicity of compound 1 was evaluated by methyl thiazolyl tetrazolium(MTT)assay using doxorubicin as a positive control.Compound 1 showed weak antiproliferative activity against human lung carcinoma cell line A549(IC50~22.6μmol/L),and the substitution at C16 was critical for the cytotoxicity of compound 1.In addition,the biosynthetic gene cluster of compound 1 was identified and the biosynthetic pathway of compound 1 was proposed.