Natalamycin A, an ansamycin from a termite-associated Streptomyces sp.

被引：81

作者：

Kim, Ki Hyun ^{[1
,3
]}

Ramadhar, Timothy R. ^{[1
]}

Beemelmanns, Christine ^{[1
]}

Cao, Shugeng ^{[1
]}

Poulsen, Michael ^{[2
]}

Currie, Cameron R. ^{[2
]}

Clardy, Jon ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA

[3] Sungkyunkwan Univ, Sch Pharm, Nat Prod Res Lab, Suwon 440 746, South Korea

来源：

CHEMICAL SCIENCE | 2014年 / 5卷 / 11期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

BENZOQUINONE ANSAMYCINS; GELDANAMYCIN; BIOSYNTHESIS; SYMBIONTS; 19-S-METHYLGELDANAMYCIN; IDENTIFICATION; CONFORMATIONS; INHIBITION; POLYKETIDE; PREDICTION;

D O I：

10.1039/c4sc01136h

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We report a preliminary functional and complete structural characterization of a highly unusual geldanamycin analog, natalamycin A, that was isolated from Streptomyces strain M56 recovered from a South African nest of Macrotermes natalensis termites. Bioassay-guided fractionation based on antifungal activity led to the isolation of natalamycin A, and a combination of NMR spectroscopy and X-ray crystallographic analysis, including highly-accurate quantum-chemical NMR calculations on the largest and most conformationally-flexible system to date, revealed natalamycin A's three-dimensional solid-and solution-state structure. This structure along with the structures of related compounds isolated from the same source suggest a geldanamycin-like biosynthetic pathway with unusual post-PKS modifications.

引用

页码：4333 / 4338

页数：6

共 45 条

[11] Targeting heat-shock-protein 90 (Hsp90) by natural products: geldanamycin, a show case in cancer therapy [J].