A new cytotoxic epothilone from modified polyketide synthases heterologously expressed in Myxococcus xanthus

被引：41

作者：

Arslanian, RL

Tang, L

Blough, S

Ma, W

Qiu, RG

Katz, L

Carney, JR

机构：

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

[2] Kosan Biosci Inc, Dept Proc Sci, Hayward, CA 94545 USA

[3] Kosan Biosci Inc, Dept Sci Biol, Hayward, CA 94545 USA

[4] Kosan Biosci Inc, Dept Pharmacol, Hayward, CA 94545 USA

来源：

JOURNAL OF NATURAL PRODUCTS | 2002年 / 65卷 / 07期

关键词：

D O I：

10.1021/np020120f

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

A new epothilone, 10,11-didehydroepothilone D (5), was isolated from a strain of the. heterologous host Myxococcus xanthus genetically engineered to produce epothilone D (4). The structure of 5 was determined from NMR and MS data. The epothilone polyketide synthase was further modified in a recombinant M. xanthus strain to produce 5 as the major epothilone-related metabolite. The cytotoxicity of 5 against a panel of tumor cell lines, including several with multidrug resistance, and its effect on tubulin polymerization were comparable to epothilone D (4).

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页码：1061 / 1064

页数：4

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