链霉菌CB03234-S中天赐霉素衍生物的发现
收稿日期: 2021-11-10
修回日期: 2021-12-09
网络出版日期: 2021-12-31
基金资助
国家自然科学基金(81872779); 天然药物及仿生药物国家重点实验室开放基金(K202116)
Discovery of Tiancimycin Congeners from Streptomyces sp. CB03234-S
Received date: 2021-11-10
Revised date: 2021-12-09
Online published: 2021-12-31
Supported by
National Science Foundation of China(81872779); State Key Laboratory of Natural and Biomimetic Drugs(K202116)
天赐霉素是一种蒽醌骈合型烯二炔类化合物, 具有显著的抗肿瘤活性. 通过在天赐霉素A高产菌株放线菌CB03234-S中异源表达两个细胞色素P450羟化酶基因dynE10和dynOrf19, 分离得到三个天赐霉素衍生物1~3. 通过一维和二维核磁共振、高分辨质谱和圆二色谱测定了它们的化学结构. 天赐霉素H (1)为天赐霉素D的C-9羟基化产物, TNM T1 (2)为一个烯二炔的环化产物, TNM T3 (3)为已知化合物. 化合物1对所有四种测试的肿瘤细胞株, 如HeLa细胞、MB49细胞、B16细胞和BIU87细胞均具有较强的抗肿瘤活性.
关键词: 天赐霉素; 蒽醌骈合型烯二炔; 细胞色素P450羟化酶; 抗肿瘤活性; 异源表达
薛露 , 张丽花 , 张成玉 , 赵鑫 , 党伟帆 , 王昭昕 , 王春华 , 所同川 , 颜晓晖 . 链霉菌CB03234-S中天赐霉素衍生物的发现[J]. 有机化学, 2022 , 42(4) : 1241 -1247 . DOI: 10.6023/cjoc202111018
Tiancimycins (TNMs) are anthraquinone-fused enediynes with phenomenal antitumor activity. By heterologous expression of two cytochrome P450 hydroxylase genes, dynE10 and dynOrf19, in the TNMs high-producing strain Streptomyces sp. CB03234-S, three TNM derivatives 1~3 were isolated. Their chemical structures were determined by one-dimensional and two-dimensional NMR, high resolution mass spectrometry and circular dichroism. TNM H (1) is the C-9-hydroxylated product of TNM D, TNM T1 (2) is a cycloaromatized product, and TNM T3 (3) is a known compound. Compound 1 exhibited strong antitumor activity against the four tested cancer cell lines, including HeLa, MB49, B16 and BIU87.
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