摘要/Abstract

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40 μg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（IC₅₀~22.6 μmol/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.
关键词: 链霉菌, 天然产物, 多环特特拉姆酸大环内酰胺, 生物合成
Montamide A (1), a new polycyclic tetramate macrolactam (PoTeM) with a 5/5/6 tricyclic system was isolated from recombinant strain S001-PoTeM_S023, which is derived from Streptomyces sp. S001 by introducing a new PoTeM biosynthetic gene cluster cft_S023. 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 40 μg/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 (IC₅₀~22.6 μmol/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.
Key words: streptomyces, natural products, policyclic tetramate macrolactams, biosynthesis


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