Ishikawa Fumihiro, Nakamura Shinya, Nakanishi Isao, Tanabe Genzoh
Faculty of Pharmacy, Kindai University, Osaka, Japan.
J Pept Sci. 2024 Mar;30(3):e3545. doi: 10.1002/psc.3545. Epub 2023 Sep 18.
Nonribosomal peptide synthetases (NRPSs) biosynthesize nonribosomal peptide (NRP) natural products, which belong to the most promising resources for drug discovery and development because of their wide range of therapeutic applications. The results of genetic, biochemical, and bioinformatics analyses have enhanced our understanding of the mechanisms of the NRPS machinery. A major goal in NRP biosynthesis is to reprogram the NRPS machinery to enable the biosynthetic production of designed peptides. Reprogramming strategies for the NRPS machinery have progressed considerably in recent years, thereby increasing the yields and generating modified peptides. Here, the recent progress in NRPS reprogramming and its application in peptide synthesis are described.
非核糖体肽合成酶(NRPSs)负责生物合成非核糖体肽(NRP)天然产物,由于其广泛的治疗应用,这些产物属于药物发现和开发中最具前景的资源。遗传、生化和生物信息学分析的结果增进了我们对NRPS机制的理解。NRP生物合成的一个主要目标是对NRPS机制进行重新编程,以实现设计肽的生物合成生产。近年来,NRPS机制的重新编程策略取得了显著进展,从而提高了产量并生成了修饰肽。在此,将描述NRPS重新编程的最新进展及其在肽合成中的应用。