Genetic engineering of antibiotic biosynthesis for the generation of new aminocoumarins

Genetic engineering of antibiotic biosynthesis for the generation of new aminocoumarins
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DOI:
10.1016/j.biotechadv.2009.05.017
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发表时间:
2009-11-01
影响因子:
16
通讯作者:
Heide, Lutz
Heide, Lutz
中科院分区:
工程技术1区
文献类型:
--
作者:
Heide, Lutz

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氨基香豆素类抗生素新生霉素。clorobiocin和香豆霉素A是促旋酶的抑制剂和高效抗菌剂。它们的生物合成基因簇已经从各自的链霉菌生产菌株中克隆,并且其中包含的几乎所有基因的功能已经通过遗传和生物化学方法阐明。已经开发了有效的方法用于基因操作和簇的异源表达,并且已经通过代谢工程、突变合成和化学酶促合成产生了100多种这些抗生素的新衍生物。为遗传和基因组方法产生新的生物活性化合物的能力提供了一个模型。(C)2009 Elsevier Inc.版权所有
The aminocoumarin antibiotics novobiocin. clorobiocin and coumermycin A, are inhibitors of gyrase and highly effective antibacterial agents Their biosynthetic gene clusters have been cloned from the respective Streptomyces producer strains, and the function of nearly all genes contained therein has been elucidated by genetic and biochemical methods. Efficient methods have been developed for the genetic manipulation and the heterologous expression of the clusters, and more than 100 new derivatives of these antibiotics have been generated by metabolic engineering, mutasynthesis and chemoenzymatic synthesis. providing a model for the power of genetic and genomic methods for the generation of new bioactive compounds. (C) 2009 Elsevier Inc. All rights reserved