Production of 8-demethylgeldanamycin and 4,5-epoxy-8-demethylgeldanamycin from a recombinant strain of Streptomyces hygroscopicus

被引：19

作者：

Buchanan, GO ^{[1
]}

Regentin, R ^{[1
]}

Piagentini, M ^{[1
]}

Rascher, A ^{[1
]}

McDaniel, R ^{[1
]}

Galazzo, JL ^{[1
]}

Licari, PJ ^{[1
]}

机构：

[1] Kosan Biosci Inc, Hayward, CA 94545 USA

来源：

JOURNAL OF NATURAL PRODUCTS | 2005年 / 68卷 / 04期

关键词：

D O I：

10.1021/np0496744

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Two new geldanamycin derivatives produced by genetic engineering of Streptomyces hygroscopicus strain K309-27-1 were isolated and characterized. Removal of the 8-methyl group of geldanamycin was achieved by replacing the AT4 domain of the polyketide synthase with a malonyl AT domain. The resulting strain produced 8-demethyl geldanamycin (2) and 4,5-epoxy-8-demethylgeldanamycin (3). The structures of both molecules were elucidated through interpretation of 1D and 2D NMR data as well, as comparison with authentic geldanamycin derivatives. Compounds 2 and 3 displayed moderate cytotoxicity against the human breast cancer cell line SK-BR-3.

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页码：607 / 610

页数：4

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