新多环特特拉姆酸大环内酰胺3-Hydroxycombamide I的发现
收稿日期: 2021-10-02
修回日期: 2022-01-14
网络出版日期: 2022-01-21
基金资助
国家自然科学基金(81773598); 山东大学青年学者计划(2016WLJH31); 长江学者和创新团队发展计划(IRT_17R68)
Discovery of a New Polycyclic Tetramate Macrolactam 3-Hydroxycombamide I
Received date: 2021-10-02
Revised date: 2022-01-14
Online published: 2022-01-21
Supported by
National Natural Science Foundation of China(81773598); Young Scholars Program of Shandong University(2016WLJH31); Program for Changjiang Scholars and Innovative Research Team in University(IRT_17R68)
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(PoTeMs)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100 μmol/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PoTeMs的C-3位羟基化修饰可能发生在多环体系氧化修饰之后.
关键词： 天然产物; 生物转化; 链霉菌; 多环特特拉姆酸大环内酰胺
颜雅倩 , 王浩鑫 , 李瑶瑶 . 新多环特特拉姆酸大环内酰胺3-Hydroxycombamide I的发现[J]. 有机化学, 2022 , 42(5) : 1557 -1561 . DOI: 10.6023/cjoc202110001
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.
| [1] | Cao, S.; Blodgett, J.; Clardy, J. Org. Lett. 2010, 12, 4652. |
| [2] | Zhang, G.; Zhang, W.; Saha, S.; Zhang, C. Curr. Top. Med. Chem. 2016, 16, 1727. |
| [3] | Liu, Y.; Wang, H.; Song, R.; Chen, J.; Li, T.; Li, Y.; Du, L.; Shen, Y. Org. Lett. 2018, 20, 3504. |
| [4] | Blodgett, J.; Oh, D.; Cao, S.; Currie, C.; Kolter, R.; Clardy, J. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 11692. |
| [5] | Yu, F.; Zaleta-Rivera, K.; Zhu, X.; Huffman, J.; Millet, J.; Harris, S.; Yuen, G.; Li, X.; Du, L. Antimicrob. Agents Chemother. 2007, 51, 64. |
| [6] | Li, Y.; Wang, H.; Liu, Y.; Jiao, Y.; Li, S.; Shen, Y.; Du, L. Angew. Chem., Int. Ed. 2018, 57, 6221. |
| [7] | Saha, S.; Zhang, W.; Zhang, G.; Zhu, Y.; Chen, Y.; Liu, W.; Yuan, C.; Zhang, Q.; Zhang, H.; Zhang, L.; Zhang, W.; Zhang, C. Chem. Sci. 2017, 8, 1607. |
| [8] | Zhang, G.; Zhang, W.; Zhang, Q.; Shi, T.; Ma, L.; Zhu, Y.; Li, S.; Zhang, H.; Zhao, Y.; Shi, R.; Zhang, C. Angew. Chem., Int. Ed. 2014, 53, 4840. |
| [9] | Qi, Y.; Ding, E.; Blodgett, J. ACS Synth. Biol. 2018, 7, 357. |
| [10] | Yu, H.; Jiang, S.; Bu, X.; Wang, J.; Weng, J.; Yang, X.; He, K.; Zhang, Z.; Ao, P.; Xu, J.; Xu, M. Sci. Rep. 2017, 7, 40689. |
| [11] | Li, Y.; Huffman, J.; Li, Y.; Du, L.; Shen, Y. MedChemComm 2012, 3, 982. |
| [12] | Greunke, C.; Antosch, J.; Gulder, T. Chem. Commun. 2015, 51, 5334. |
| [13] | Yan, Y.; Wang, H.; Song, Y.; Zhu, D.; Shen, Y.; Li, Y. ACS Synth. Biol. 2021, 10, 2434. |
| [14] | Jin, H.; Zhang, W.; Zhang, G.; Zhang, L.; Liu, W.; Zhang, C. Org. Lett. 2020, 22, 1731. |
| [15] | Zhang, W.; Zhang, G.; Zhang, L.; Liu, W.; Jiang, X.; Jin, H.; Liu, Z.; Zhang, H.; Zhou, A.; Zhang, C. Tetrahedron 2018, 74, 6839. |
| [16] | Jiao, Y.; Yan, Y.; Liu, Y.; Zhu, D.; Shen, Y.; Li, Y. Chin. J. Org. Chem. 2020, 40, 1779. (in Chinese) |
| [16] | (焦玉杰, 颜雅倩, 刘焱, 朱德裕, 沈月毛, 李瑶瑶, 有机化学, 2020, 40, 1779.) |
| [17] | Mosmann, T. J. Immunol. Methods 1983, 65, 55. |
| [18] | Li, J.; Lv, C.; Sun, W.; Li, Z.; Han, X.; Li, Y.; Shen, Y. Antimicrob. Agents Chemother. 2013, 57, 2191. |
/
| 〈 |
|
〉 |
