Isolation and characterization of novel geldanamycin analogues

被引:17
作者
Hu, ZH [1 ]
Liu, YQ [1 ]
Tian, ZQ [1 ]
Ma, W [1 ]
Starks, CM [1 ]
Regentin, R [1 ]
Licari, P [1 ]
Myles, DC [1 ]
Hutchinson, CR [1 ]
机构
[1] Kosan Biosci Inc, Hayward, CA 94545 USA
关键词
D O I
10.7164/antibiotics.57.421
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:421 / 428
页数:8
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