Weber T, Welzel K, Pelzer S, Vente A, Wohlleben W
Department of Microbiology/Biotechnology, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
J Biotechnol. 2003 Dec 19;106(2-3):221-32. doi: 10.1016/j.jbiotec.2003.08.004.
Streptomycetes are the most important bacterial producers of bioactive secondary metabolites such as antibiotics or cytostatics. Due to the emerging resistance of pathogenic bacteria to all commonly used antibiotics, new and modified natural compounds are required for the development of novel drugs. In addition to the classical screening for natural compounds, genome driven approaches like combinatorial biosynthesis are permanently gaining relevance for the generation of new structures. This technology utilizes the combination of genes from different biosynthesis pathways resulting in the production of novel or modified metabolites. The basis for this strategy is the access to a significant number of genes and the knowledge about the activity and specificity of the enzymes encoded by them. A joint initiative was started to exploit the biosynthesis gene clusters from streptomycetes. In this publication, an overview of the strategy for the identification and characterization of numerous biosynthesis gene clusters for polyketides displaying interesting functions and particular structural features is given.
链霉菌是生物活性次级代谢产物(如抗生素或细胞抑制剂)最重要的细菌生产者。由于病原菌对所有常用抗生素的耐药性不断出现,开发新型药物需要新的和经过修饰的天然化合物。除了传统的天然化合物筛选方法外,像组合生物合成这样的基因组驱动方法在生成新结构方面的相关性也在不断增加。这项技术利用来自不同生物合成途径的基因组合,从而产生新的或经过修饰的代谢产物。该策略的基础是获得大量基因以及了解它们所编码酶的活性和特异性。一项联合倡议已启动,旨在利用链霉菌的生物合成基因簇。在本出版物中,给出了用于鉴定和表征众多具有有趣功能和特定结构特征的聚酮化合物生物合成基因簇的策略概述。