Mutasynthesis of aureonitrile: An aureothin derivative with significantly improved cytostatic effect

被引:46
作者
Ziehl, M [1 ]
He, J [1 ]
Dahse, HM [1 ]
Hertweck, C [1 ]
机构
[1] Hans Knoell Inst Nat Prod Res, D-07745 Jena, Germany
关键词
antitumor agents; mutasynthesis; natural products; polyketides;
D O I
10.1002/anie.200461990
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Tapping nature's biosynthetic potential: Formation of the rare p-nitro benzoate precursor of aureothin, a mixed polyketide metabolite of Streptomyces thioluteus, requires two key enzymes: a p-amino benzoate synthase and an N-oxygenase. Feeding of surrogates to engineered block mutants (e.g. S. lividans ZX1::pHJ97) reveals that the iterative modular aureothin polyketide also accepts p-cyano benzoate as the starter, which is subsequently processed to the nitrile analogue of aureothin, aureonitrile, which has improved cytostatic properties. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
引用
收藏
页码:1202 / 1205
页数:4
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