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The hidden enzymology of bacterial natural product biosynthesis
Nature Reviews Chemistry ( IF 38.1 ) Pub Date : 2019-06-12 , DOI: 10.1038/s41570-019-0107-1
Thomas A. Scott , Jörn Piel

Bacterial natural products display astounding structural diversity, which, in turn, endows them with a remarkable range of biological activities that are of significant value to modern society. Such structural features are generated by biosynthetic enzymes that construct core scaffolds or perform peripheral modifications, and can thus define natural product families, introduce pharmacophores and permit metabolic diversification. Modern genomics approaches have greatly enhanced our ability to access and characterize natural product pathways via sequence-similarity-based bioinformatics discovery strategies. However, many biosynthetic enzymes catalyse exceptional, unprecedented transformations that continue to defy functional prediction and remain hidden from us in bacterial (meta)genomic sequence data. In this Review, we highlight exciting examples of unusual enzymology that have been uncovered recently in the context of natural product biosynthesis. These suggest that much of the natural product diversity, including entire substance classes, awaits discovery. New approaches to lift the veil on the cryptic chemistries of the natural product universe are also discussed.



中文翻译:

细菌天然产物生物合成的隐藏酶

细菌天然产物显示出惊人的结构多样性,这反过来又赋予它们大量的生物活动,这些活动对现代社会具有重要的价值。此类结构特征是由构建核心支架或进行外围修饰的生物合成酶产生的,因此可以定义天然产物家族,引入药效团并允许代谢多样化。现代基因组学方法极大地增强了我们通过基于序列相似性的生物信息学发现策略访问和表征天然产物途径的能力。然而,许多生物合成酶催化异常的,空前的转化,这些转化继续违背功能预测,并在细菌(元)基因组序列数据中仍然对我们隐藏。在这篇评论中,我们重点介绍了在天然产物生物合成的背景下最近发现的不寻常酶学的令人兴奋的例子。这些表明,许多天然产物的多样性,包括整个物质类别,都有待发现。还讨论了在天然产物宇宙的神秘化学上揭开面纱的新方法。

更新日期:2019-11-18
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