新多环大环内酰胺Clifednamide K的发现
收稿日期: 2021-09-26
修回日期: 2021-12-24
网络出版日期: 2022-01-11
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 Clifednamide K
Received date: 2021-09-26
Revised date: 2021-12-24
Online published: 2022-01-11
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)
利用组合生物合成策略构建了人工杂合多环特特拉姆酸大环内酰胺(PoTeM)基因簇, 并从异源表达重组菌株SR111-cbmA- OX1-cftC中分离得到2个PoTeM类化合物preikarugamycin (1)和clifednamide K (2). 通过核磁共振和高分辨质谱分析确定化合物1为ikarugamycin生物合成中间体, 化合物2为结构新颖的5/6双环PoTeM. 采用滤纸片法测定了化合物1和2的抗细菌和抗真菌活性, 结果显示二者在20 μg载药量下均无抗菌活性. 采用噻唑蓝比色法(MTT)测定了化合物1和2的细胞毒活性, 结果显示化合物1对人肝癌细胞HepG-2和人乳腺癌细胞MCF-7具有较强细胞毒活性, 半抑制浓度(IC50)分别为3.34和2.72 μmol/L, 化合物2对测试细胞株无明显细胞毒活性.
罗洁 , 颜雅倩 , 王浩鑫 , 李瑶瑶 . 新多环大环内酰胺Clifednamide K的发现[J]. 有机化学, 2022 , 42(4) : 1224 -1228 . DOI: 10.6023/cjoc202109042
The artificial hybrid polycyclic tetramate macrolactam (PoTeM) gene cluster was constructed through combinatory biosynthesis approach and two PoTeMs, preikarugamycin (1) and clifednamide K (2), were isolated from the recombinant strain SR111-cbmA-OX1-cftC. The chemical structures of 1 and 2 were determined to be the biosynthetic inermediate of ikarugamycin and a new 5/6 dicyclic PoTeM, respectively, by analysis of nuclear magnetic resonance spectroscopy (NMR) data and high resolution mass spectrometry (HRMS). The antibacterial activity of compounds 1 and 2 was tested by filter paper disc diffusion assay. The results showed that they were inactive at 20 μg/disc. The cytotoxicity of compounds 1 and 2 was evaluated by methyl thiazolyl tetrazolium (MTT) colorimetric method. Compound 1 showed potent antiproliferative activity against human liver (HepG-2) and breast cancer cell lines (MCF-7) with half maximal inhibitory concentration (IC50) values of 3.34 and 2.72 μmol/L, respectively, while compound 2 showed no cytotoxicity for the tested cell lines.
| [1] | Liu, Y.; Wang, H.; Song, R.; Chen, J.; Li, T.; Li, Y.; Du, L.; Shen, Y. Org. Lett. 2018, 20, 3504. |
| [2] | Zhang, G.; Zhang, W.; Saha, S.; Zhang, C. Curr. Top. Med. Chem. 2016, 16, 1727. |
| [3] | Ding, Y.; Li, Y.; Li, Z.; Zhang, J.; Lu, C.; Wang, H.; Shen, Y.; Du, L. Biochim. Biophys. Acta 2016, 1860, 2097. |
| [4] | Cao, S.; Blodgett, J. A.; Clardy, J. Org. Lett. 2010, 12, 4652. |
| [5] | Li, Y.; Wang, H.; Liu, Y.; Jiao, Y.; Li, S.; Shen, Y.; Du, L. Angew. Chem., Int. Ed. 2018, 57, 6221. |
| [6] | 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. |
| [7] | 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. |
| [8] | Yan, Y.; Wang, H.; Song, Y.; Zhu, D.; Shen, Y.; Li, Y. ACS Synth. Biol. 2021, 10, 2434. |
| [9] | Jin, H.; Zhang, W.; Zhang, G.; Zhang, L.; Liu, W.; Zhang, C. Org. Lett. 2020, 22, 1731. |
| [10] | Greunke, C.; Antosch, J.; Gulder, T. A. M. Chem. Commun. 2015, 51, 5334. |
| [11] | Li, Y.; Huffman, J.; Li, Y.; Du, L.; Shen, Y. MedChemComm 2012, 3, 982. |
| [12] | Jiao, Y.; Liu, Y.; Wang, H.; Zhu, D.; Shen, Y.; Li, Y. J. Nat. Prod. 2020, 83, 2803. |
| [13] | 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. |
| [14] | Zhang, W.; Zhang, G.; Zhang, L.; Liu, W.; Jiang, X.; Jin, H.; Liu, Z.; Zhang, H.; Zhou, A.; Zhang, C. Tetrahedron 2018, 74, 6839. |
| [15] | Jiao, Y.; Yan, Y.; Liu, Y.; Zhu, D.; Shen, Y.; Li, Y. Chin. J. Org. Chem. 2020, 40, 1779. (in Chinese) |
| [15] | ( 焦玉杰, 颜雅倩, 刘焱, 朱德裕, 沈月毛, 李瑶瑶, 有机化学, 2020, 40, 1779.) |
| [16] | Shi, P.; Li, Y.; Zhu, J.; Shen, Y.; Wang, H. J. Nat. Prod. 2021, 84, 1924. |
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