Isolation and characterization of novel geldanamycin analogues
Isolation and characterization of novel geldanamycin analogues
复制标题
DOI：
10.7164/antibiotics.57.421
复制
发表时间：
2004-07-01
影响因子：
3.3
通讯作者：
Hutchinson, CR
中科院分区：
文献类型：
--
作者：
Hu, ZH;Liu, YQ;Hutchinson, CR
分离和鉴定了微生物直接转化产生的具有新结构的新型格尔达霉素类似物和一株基因工程格尔达霉素生产菌。在吸水链霉菌AM-3672的生长培养液中加入15-羟基格尔丹霉素，得到3个化合物：15-羟基格尔丹霉素，三环格尔丹霉素类似物(KOSN-1633)和格尔丹霉素甲酯(1)。从吸湿链霉菌NRRL 3602/pKOS279-78中分离得到两个相关化合物，分别为17-甲酰基-17-去甲氧基-18-O、-21-O-二氢格尔达霉素和17-羟甲基-17-脱甲氧基格尔达霉素。与格尔达霉素相比，这五个新化合物对SKBr3癌细胞的细胞毒性降低。
New geldanamycin analogues with novel structures arising from direct microbial bioconversion and a genetically engineered geldanamycin producer were isolated and characterized. Three compounds, 15-hydroxygeldanamycin, a tricyclic geldanamycin analog (KOSN-1633), and methyl-geldanamycinate(1)), were isolated after geldanamycin was added to a growing culture of the herbimycin producing strain-Streptomyces hygroscopicus AM-3672. Two related compounds, 17-formyl-17-demethoxy-18-O,-21-O-dihydrogeldanamycin and 17-hydroxymethyl-17-demethoxygeldanamycin were isolated from S. hygroscopicus NRRL 3602/pKOS279-78, a geldanamycin-producing strain containing various genes isolated from S. hygroscopicus AM-3672. Compared with geldanamycin, these five new compounds exhibited reduced cytotoxicity against SKBr3 cancer cells.