Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland.
Nat Rev Drug Discov. 2022 May;21(5):359-378. doi: 10.1038/s41573-022-00414-6. Epub 2022 Mar 16.
Bacteria provide a rich source of natural products with potential therapeutic applications, such as novel antibiotic classes or anticancer drugs. Bioactivity-guided screening of bacterial extracts and characterization of biosynthetic pathways for drug discovery is now complemented by the availability of large (meta)genomic collections, placing researchers into the postgenomic, big-data era. The progress in next-generation sequencing and the rise of powerful computational tools provide unprecedented insights into unexplored taxa, ecological niches and 'biosynthetic dark matter', revealing diverse and chemically distinct natural products in previously unstudied bacteria. In this Review, we discuss such sources of new chemical entities and the implications for drug discovery with a particular focus on the strategies that have emerged in recent years to identify and access novelty.
细菌是天然产物的重要来源，具有潜在的治疗应用，例如新型抗生素或抗癌药物。现在，通过活性导向筛选细菌提取物和鉴定生物合成途径来发现药物，再结合大量（宏）基因组文库，研究人员进入了后基因组、大数据时代。新一代测序的进步和强大计算工具的兴起，为未开发的分类群、生态位和“生物合成暗物质”提供了前所未有的见解，揭示了以前未研究过的细菌中多样化和化学性质不同的天然产物。在这篇综述中，我们讨论了这些新化学实体的来源及其对药物发现的影响，特别关注了近年来出现的用于识别和获取新颖性的策略。
