Wang Mengjiao, Fage Christopher D, He Yile, Mi Jinhui, Yang Yang, Li Fei, An Xiaoping, Fan Huahao, Song Lihua, Zhu Shaozhou, Tong Yigang
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Department of Chemistry, University of Warwick, Coventry, United Kingdom.
Front Bioeng Biotechnol. 2021 Sep 24;9:741364. doi: 10.3389/fbioe.2021.741364. eCollection 2021.
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing family of natural products that exhibit a range of structures and bioactivities. Initially assembled from the twenty proteinogenic amino acids in a ribosome-dependent manner, RiPPs assume their peculiar bioactive structures through various post-translational modifications. The essential modifications representative of each subfamily of RiPP are performed on a precursor peptide by the so-called processing enzymes; however, various tailoring enzymes can also embellish the precursor peptide or processed peptide with additional functional groups. Lasso peptides are an interesting subfamily of RiPPs characterized by their unique lariat knot-like structure, wherein the C-terminal tail is inserted through a macrolactam ring fused by an isopeptide bond between the N-terminal amino group and an acidic side chain. Until recently, relatively few lasso peptides were found to be tailored with extra functional groups. Nevertheless, the development of new routes to diversify lasso peptides and thus introduce novel or enhanced biological, medicinally relevant, or catalytic properties is appealing. In this review, we highlight several strategies through which lasso peptides have been successfully modified and provide a brief overview of the latest findings on the tailoring of these peptides. We also propose future directions for lasso peptide tailoring as well as potential applications for these peptides in hybrid catalyst design.
核糖体合成及翻译后修饰肽（RiPPs）是一类不断发展的天然产物家族，具有多种结构和生物活性。RiPPs最初以核糖体依赖的方式由20种蛋白质ogenic氨基酸组装而成，通过各种翻译后修饰形成其独特的生物活性结构。RiPP各亚家族的代表性关键修饰由所谓的加工酶在前体肽上进行；然而，各种修饰酶也可以用额外的官能团修饰前体肽或加工后的肽。套索肽是RiPPs中一个有趣的亚家族，其特征在于独特的套索状结构，其中C末端尾巴通过由N末端氨基和酸性侧链之间的异肽键融合而成的大环内酰胺环插入。直到最近，发现用额外官能团修饰的套索肽相对较少。然而，开发使套索肽多样化从而引入新的或增强的生物学、医学相关或催化特性的新途径很有吸引力。在这篇综述中，我们重点介绍了几种成功修饰套索肽的策略，并简要概述了这些肽修饰的最新发现。我们还提出了套索肽修饰的未来方向以及这些肽在杂化催化剂设计中的潜在应用。
