链霉菌CB03234-S中天赐霉素衍生物的发现

Discovery of Tiancimycin Congeners from Streptomyces sp.CB03234-S

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.

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.