Wu Chunyu, van der Donk Wilfred A
Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 S Mathews Ave, Urbana, IL 61801, United States.
Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 S Mathews Ave, Urbana, IL 61801, United States; Department of Chemistry and the Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, 600 S Mathews Ave, Urbana, IL 61801, United States.
Curr Opin Biotechnol. 2021 Jun;69:221-231. doi: 10.1016/j.copbio.2020.12.022. Epub 2021 Feb 5.
Natural products have historically been important lead sources for drug development, particularly to combat infectious diseases. Increasingly, their structurally complex scaffolds are also envisioned as leads for applications for which they did not evolve, an approach aided by engineering of new-to-nature analogs. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are promising candidates for bioengineering because they are genetically encoded and their biosynthetic enzymes display significant substrate tolerance. This review highlights recent advances in the discovery of highly unusual new reactions by genome mining and the application of engineering approaches to generate and screen novel RiPP variants. Furthermore, through the use of synthetic biology approaches, hybrid molecules with enhanced or completely new activities have been identified, which opens the door for future advancement of RiPPs as potential next-generation therapeutics.
从历史上看，天然产物一直是药物开发的重要先导来源，尤其是在对抗传染病方面。越来越多的是，它们结构复杂的支架也被设想为其未曾进化出的应用的先导，这种方法借助于新型天然类似物的工程改造。核糖体合成和翻译后修饰的肽（RiPPs）是生物工程的有前途的候选物，因为它们是基因编码的，并且它们的生物合成酶表现出显著的底物耐受性。本综述重点介绍了通过基因组挖掘发现高度不寻常的新反应以及应用工程方法生成和筛选新型RiPP变体的最新进展。此外，通过使用合成生物学方法，已经鉴定出具有增强或全新活性的杂合分子，这为RiPPs作为潜在的下一代治疗药物的未来发展打开了大门。
