Rational Biosynthetic Engineering for Optimization of Geldanamycin Analogues
Kim, Woncheol1,2; Lee, Dongho3; Hong, Seong Su3; Na, Zhu1,4,5; Shin, Jin Chul1,2; Roh, Su Heun1; Wu, Cheng-Zhu1; Choi, Oksik1; Lee, Kyeong1; Shen, Yue-Mao4; Paik, Sang-Gi2; Lee, Jung Joon1; Hong, Young-Soo1
2009-05-04
发表期刊CHEMBIOCHEM
卷号10期号:7页码:1243-1251
摘要A rational biosynthetic engineering approach was applied to the optimization of the pharmacological properties of the benzoquinone ansamycin, geldanamycin. Geldanamycin and its natural or semisynthetic derivatives have the potential to serve as anticancer chemotherapeutic agents. However, these first-generation Hsp90 inhibitors share an unfavorable structural feature that causes both reduced efficacy and toxicity during clinical evaluation. We report the rationally designed biosynthesis of C15 hydroxylated non-quinone geldanamycin analogues by site-directed mutagenesis of the geldanamycin polyketide synthase (PKS), together with a combination of post-PKS tailoring genes. A 15-hydroxyl-17-demethoxy non-quinone analogue, DHQ3, exhibited stronger inhibition of Hsp90 ATPase activity (4.6-fold) than geldanamycin. Taken together, the results of the present study indicate that rational biosynthetic engineering allows the generation of derivatives of geldanamycin with superior pharmacological properties.
关键词Biosynthesis Geldanamycin Natural Products Polyketides Site-directed Mutagenesis
学科领域Biochemistry & Molecular Biology ; Chemistry, Medicinal
DOI10.1002/cbic.200800763
收录类别SCI
语种英语
WOS记录号WOS:000266382900016
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/14557
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Korea Res Inst Biosci & Biotechnol, Taejon 305806, South Korea
2.Chungnam Natl Univ, Taejon 305764, South Korea
3.Korea Univ, Sch Life Sci & Biotechnol, Seoul 136713, South Korea
4.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources W China, Kunming Inst Bot, Kunming 650204, Peoples R China
5.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714
Kim, Woncheol,Lee, Dongho,Hong, Seong Su,et al. Rational Biosynthetic Engineering for Optimization of Geldanamycin Analogues[J]. CHEMBIOCHEM,2009,10(7):1243-1251.
APA Kim, Woncheol.,Lee, Dongho.,Hong, Seong Su.,Na, Zhu.,Shin, Jin Chul.,...&Hong, Young-Soo.(2009).Rational Biosynthetic Engineering for Optimization of Geldanamycin Analogues.CHEMBIOCHEM,10(7),1243-1251.
MLA Kim, Woncheol,et al."Rational Biosynthetic Engineering for Optimization of Geldanamycin Analogues".CHEMBIOCHEM 10.7(2009):1243-1251.
条目包含的文件 下载所有文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
BJ01257365.pdf(578KB) 开放获取--浏览 下载
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Kim, Woncheol]的文章
[Lee, Dongho]的文章
[Hong, Seong Su]的文章
百度学术
百度学术中相似的文章
[Kim, Woncheol]的文章
[Lee, Dongho]的文章
[Hong, Seong Su]的文章
必应学术
必应学术中相似的文章
[Kim, Woncheol]的文章
[Lee, Dongho]的文章
[Hong, Seong Su]的文章
相关权益政策
暂无数据
收藏/分享
文件名: BJ01257365.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。