Scott Thomas A, Piel Jörn
Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
Nat Rev Chem. 2019 Jul;3(7):404-425. doi: 10.1038/s41570-019-0107-1. Epub 2019 Jun 12.
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.
细菌天然产物展现出惊人的结构多样性，这进而赋予它们一系列显著的生物活性，对现代社会具有重要价值。这些结构特征由构建核心骨架或进行外围修饰的生物合成酶产生，因此可以定义天然产物家族、引入药效基团并实现代谢多样化。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来获取和表征天然产物途径的能力。然而，许多生物合成酶催化特殊的、前所未有的转化，这些转化仍然难以进行功能预测，并且在细菌（宏）基因组序列数据中对我们来说仍然是隐藏的。在本综述中，我们重点介绍了最近在天然产物生物合成背景下发现的不寻常酶学的激动人心的例子。这些表明，许多天然产物的多样性，包括整个物质类别，仍有待发现。我们还讨论了揭开天然产物世界隐秘化学面纱的新方法。
