新型格尔德霉素类似物的分离与表征

Isolation and characterization of novel geldanamycin analogues.

作者信息

Hu Zhihao, Liu Yaoquan, Tian Zong-Qiang, Ma Wei, Starks Courtney M, Regentin Rika, Licari Peter, Myles David C, Hutchinson C Richard

机构信息

Kosan Biosciences, Inc., 3832 Bay Center Place Hayward, CA 94545 USA.

出版信息

J Antibiot (Tokyo). 2004 Jul;57(7):421-8. doi: 10.7164/antibiotics.57.421.

DOI:10.7164/antibiotics.57.421

PMID:15376554

Abstract

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), 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.

摘要

通过直接微生物生物转化和基因工程改造的格尔德霉素产生菌，分离并鉴定了具有新型结构的新型格尔德霉素类似物。在将格尔德霉素添加到除草霉素产生菌株——吸水链霉菌AM - 3672的生长培养物中后，分离出了三种化合物，即15 - 羟基格尔德霉素、一种三环格尔德霉素类似物（KOSN - 1633）和格尔德霉素甲酯。从吸水链霉菌NRRL 3602/pKOS279 - 78中分离出了两种相关化合物，即17 - 甲酰基 - 17 - 去甲氧基 - 18 - O，- 21 - O - 二氢格尔德霉素和17 - 羟甲基 - 17 - 去甲氧基格尔德霉素，该菌株是一种产生格尔德霉素的菌株，含有从吸水链霉菌AM - 3672中分离出的各种基因。与格尔德霉素相比，这五种新化合物对SKBr3癌细胞的细胞毒性降低。