Bioinformatics Group, Wageningen University, Droevendaalsesteeg 1, Radix West, Building 107, 6708 PB Wageningen, The Netherlands.
Molecular Genetics, University of Groningen, Nijenborgh 7, 9726AG Groningen, The Netherlands.
FEMS Microbiol Rev. 2017 May 1;41(3):417-429. doi: 10.1093/femsre/fux014.
The bacterial kingdom provides a major source of antimicrobials that can either be directly applied or used as scaffolds to further improve their functionality in the host. The rapidly increasing amount of bacterial genomic, metabolomic and transcriptomic data offers unique opportunities to apply a variety of approaches to mine for existing and novel antimicrobials. Here, we discuss several powerful mining approaches to identify novel molecules with antimicrobial activity across structurally diverse natural products, including ribosomally synthesized and posttranslationally modified peptides, nonribosomal peptides and polyketides. We not only discuss the direct mining of genomes based on identification of biosynthetic gene clusters, but also describe more advanced and integrative approaches in ecology-based mining, functionality-based mining and mode-of-action-based mining. These efforts are likely to accelerate the discovery and development of novel antimicrobial drugs.
细菌王国为抗菌药物提供了主要来源，可以直接应用，也可以作为支架进一步提高其在宿主中的功能。细菌基因组、代谢组学和转录组学数据的快速增加为应用各种方法来挖掘现有和新型抗菌药物提供了独特的机会。在这里，我们讨论了几种强大的挖掘方法，以识别具有抗菌活性的结构多样的天然产物中的新型分子，包括核糖体合成和翻译后修饰的肽、非核糖体肽和聚酮。我们不仅讨论了基于生物合成基因簇鉴定的基因组直接挖掘，还描述了基于生态学的挖掘、基于功能的挖掘和基于作用模式的挖掘等更先进和综合的方法。这些努力可能会加速新型抗菌药物的发现和开发。
