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2020 , Vol. 40 >Issue 6: 1779 - 1784

DOI: https://doi.org/10.6023/cjoc201912017

研究简报

链霉菌S001代谢产生的多环特特拉姆酸大环内酰胺

  • 焦玉杰 ,
  • 颜雅倩 ,
  • 刘焱 ,
  • 朱德裕 ,
  • 沈月毛 ,
  • 李瑶瑶
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  • a 山东大学药学院 天然产物化学生物学教育部重点实验室 济南 250012;
    b 山东大学基础医学院 济南 250012

收稿日期: 2019-12-12

  修回日期: 2020-01-23

  网络出版日期: 2020-03-04

基金资助

国家自然科学基金（Nos.81573311，81773598）、山东大学青年学者未来计划（No.2016WLJH31）、山东大学基本科研业务费（No.2018JC004）和教育部创新团队（No.IRT_17R68）资助项目.

收起

New Polycyclic Tetramate Macrolactam from Streptomyces sp. S001

  • Jiao Yujie ,
  • Yan Yaqian ,
  • Liu Yan ,
  • Zhu Deyu ,
  • Shen Yuemao ,
  • Li Yaoyao
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  • a Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012;
    b School of Basic Medical Sciences, Shandong University, Jinan 250012

Received date: 2019-12-12

  Revised date: 2020-01-23

  Online published: 2020-03-04

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 81573311, 81773598), the Young Scholars Program of Shandong University (No. 2016WLJH31), the Fundamental Research Funds of Shandong University (No. 2018JC004) and the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT_17R68).

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摘要

从链霉菌S001的重组菌株S001-PoTeMS023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

本文引用格式

焦玉杰 , 颜雅倩 , 刘焱 , 朱德裕 , 沈月毛 , 李瑶瑶 . 链霉菌S001代谢产生的多环特特拉姆酸大环内酰胺[J]. 有机化学, 2020 , 40(6) : 1779 -1784 . DOI: 10.6023/cjoc201912017

Abstract

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 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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