链霉菌LZ35中Germicidin糖苷的发现
收稿日期: 2021-01-21
修回日期: 2021-02-10
网络出版日期: 2021-02-26
基金资助
国家重点研发计划项目(2019YFA0905400); 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 Germicidin Glucuronides from Streptomyces sp. LZ35
Received date: 2021-01-21
Revised date: 2021-02-10
Online published: 2021-02-26
Supported by
National Key Research and Development Program(2019YFA0905400); Young Scholars Program of Shandong University(2016WLJH31); Program for Changjiang Scholars and Innovative Research Team in University(IRT_17R68)
利用培养基筛选策略从链霉菌LZ35的主产物敲除突变株SR111中分离得到2个新germicidin糖苷衍生物, 通过一维和二维核磁及高分辨质谱等数据分析确定其化学结构分别为germicidin A-4-O-β-D-glucuronide (1)和germicidin D-4-O-β-D-glucuronide (2). 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, 结果显示两者在20 μg条件下均无抗菌活性. 采用噻唑蓝比色法测定了化合物 1和2的细胞毒活性, 结果显示两者对肝癌细胞HepG2和宫颈癌细胞HeLa均无明显活性. 本研究发现了含有葡萄糖醛酸基团的germicidin衍生物, 丰富了该类化合物的结构多样性.
关键词: 链霉菌; 天然产物; 培养基筛选; germicidins
史海霞 , 李瑶瑶 , 朱敬 , 王浩鑫 , 沈月毛 . 链霉菌LZ35中Germicidin糖苷的发现[J]. 有机化学, 2021 , 41(6) : 2502 -2506 . DOI: 10.6023/cjoc202101036
Two new germicidin glucuronides were isolated from the metabolites of Streptomyces sp. SR111, which is derived from Streptomyces sp. LZ35 through deletion of eight biosynthetic gene clusters by screening of culture media. The chemicla structures of 1 and 2 were determined to be germicidin A-4-O-β-D-glucuronide and germicidin D-4-O-β-D-glucuronide, respectively, by analysis of 1-D and 2-D NMR data and high resolution mass spectrometry. The antibacterial and antifungal activities of 1 and2were eveluated by disc diffusion assay, and they showed no inhibitory activity at 20 μg/disc. The cytotoxic activities of 1 and 2 were tested by methyl thiazolyl tetrazolium (MTT) colorimetric method, and they were inactive against the HepG2 (liver cancer) and HeLa (cervical cancer) cell lines. Remarkably, compounds 1 and 2 represent the first two germicidins with a glucuronic acid moiety, which expands the structural diversity of germicidins
Key words: Streptomyces; natural products; screening of culture media; germicidins
[1] | Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2020, 83,770. |
[2] | Kalkreuter, E.; Pan, G. H.; Cepeda, A. J.; Shen, B. Trends Pharmacol. Sci. 2020, 41,13. |
[3] | Bode, H. B.; Bethe, B.; Hofs, R.; Zeeck, A. ChemBioChem 2002, 3,619. |
[4] | Zhang, J.; Li, S.; Wu, X.; Guo, Z.; Lu, C.; Shen, Y. Org. Lett. 2017, 19,2442. |
[5] | Liu, M.; Lu, C.; Shen, Y. RSC Adv. 2016, 6,49792. |
[6] | Liu, C.; Zhu, J.; Li, Y.; Zhang, J.; Lu, C.; Wang, H.; Shen, Y. ChemBioChem 2015, 16,998. |
[7] | Li, S.; Li, Y.; Lu, C.; Zhang, J.; Zhu, J.; Wang, H.; Shen, Y. Org. Lett. 2015, 17,3706. |
[8] | Zhu, J.; Chen, W.; Li, Y.; Deng, J.; Zhu, D.; Duan, J.; Liu, Y.; Shi, G.; Xie, C.; Wang, H.; Shen, Y. Gene 2014, 546,352. |
[9] | Zhao, G.; Li, S.; Wang, Y.; Hao, H.; Shen, Y.; Lu, C. Drug Discoveries Ther. 2013, 7,185. |
[10] | Li, Y.; Wang, H.; Liu, Y.; Jiao, Y.; Li, S.; Shen, Y.; Du, L. Angew. Chem., Int. Ed. 2018, 57,6221. |
[11] | Zhang, H.; Saurav, K.; Yu, Z.; Mandi, A.; Kurtan, T.; Li, J.; Tian, X.; Zhang, Q.; Zhang, W.; Zhang, C. J. Nat. Prod. 2016, 79,1610. |
[12] | Chemler, J. A.; Buchholz, T. J.; Geders, T. W.; Akey, D. L.; Rath, C. M.; Chlipala, G. E.; Smith, J. L.; Sherman, D. H. J. Am. Chem. Soc. 2012, 134,7359. |
[13] | Wilson, M. C.; Moore, B. S. Nat. Prod. Rep. 2012, 29,72. |
/
〈 |
|
〉 |