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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收藏
页码：607 / 610
页数：4
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