{"title":"Discovery, Function, and Engineering of Graspetides.","authors":"Brian Choi, A James Link","doi":"10.1016/j.trechm.2023.04.003","DOIUrl":null,"url":null,"abstract":"<p><p>Graspetides are a class of RiPPs (ribosomally synthesized and post-translationally modified peptides) defined by the presence of ester or amide side chain-side chain linkages resulting in peptide macrocycles. The graspetide name comes from the ATP-grasp enzymes that install the side chain-side chain linkages. This review covers the early, activity-based isolation of the first graspetides, marinostatins and microviridins, as well as the key genomics-driven experiments that established graspetide as RiPPs. The mechanism and structure of graspetide-associated ATP-grasp enzymes is discussed. Genome mining methods to discover new graspetides as well as the analytical techniques used to determine the linkages in graspetides are described. Extant knowledge on the bioactivity of graspetides as protease inhibitors is reviewed. Further chemical modifications to graspetides as well graspetide engineering studies are also described. We conclude with several suggestions about future directions of graspetide research.</p>","PeriodicalId":48544,"journal":{"name":"Trends in Chemistry","volume":"5 8","pages":"620-633"},"PeriodicalIF":14.0000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443899/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1016/j.trechm.2023.04.003","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/4/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Graspetides are a class of RiPPs (ribosomally synthesized and post-translationally modified peptides) defined by the presence of ester or amide side chain-side chain linkages resulting in peptide macrocycles. The graspetide name comes from the ATP-grasp enzymes that install the side chain-side chain linkages. This review covers the early, activity-based isolation of the first graspetides, marinostatins and microviridins, as well as the key genomics-driven experiments that established graspetide as RiPPs. The mechanism and structure of graspetide-associated ATP-grasp enzymes is discussed. Genome mining methods to discover new graspetides as well as the analytical techniques used to determine the linkages in graspetides are described. Extant knowledge on the bioactivity of graspetides as protease inhibitors is reviewed. Further chemical modifications to graspetides as well graspetide engineering studies are also described. We conclude with several suggestions about future directions of graspetide research.
Graspetides是一类RiPPs（核糖体合成并翻译后修饰的肽），其特征是存在酯或酰胺侧链-侧链连接，从而形成肽大环。抓取肽的名称来自于安装侧链-侧链连接的 ATP 抓取酶。这篇综述涵盖了早期基于活性分离出的首批胰凝乳肽、马林诺司他汀类和微病毒素，以及确定胰凝乳肽为 RiPPs 的关键基因组学驱动实验。还讨论了与抓药相关的 ATP 抓药酶的机制和结构。介绍了发现新grantetides的基因组挖掘方法，以及用于确定grantetides中联系的分析技术。综述了作为蛋白酶抑制剂的抓地力的生物活性方面的现有知识。此外，还介绍了对抓地力苷的进一步化学修饰以及抓地力苷工程学研究。最后，我们就grgretide 研究的未来方向提出了一些建议。
期刊介绍：
Trends in Chemistry serves as a new global platform for discussing significant and transformative concepts across all areas of chemistry. It recognizes that breakthroughs in chemistry hold the key to addressing major global challenges. The journal offers readable, multidisciplinary articles, including reviews, opinions, and short pieces, designed to keep both students and leading scientists updated on pressing issues in the field.
Covering analytical, inorganic, organic, physical, and theoretical chemistry, the journal highlights major themes such as biochemistry, catalysis, environmental chemistry, materials, medicine, polymers, and supramolecular chemistry. It also welcomes articles on chemical education, health and safety, policy and public relations, and ethics and law.
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