{"title":"吡咯糖基-tRNA 合成酶的进化:从甲烷生成到遗传密码扩展","authors":"Nikolaj G. Koch, Nediljko Budisa","doi":"10.1021/acs.chemrev.4c00031","DOIUrl":null,"url":null,"abstract":"Over 20 years ago, the pyrrolysine encoding translation system was discovered in specific archaea. Our Review provides an overview of how the once obscure pyrrolysyl-tRNA synthetase (PylRS) tRNA pair, originally responsible for accurately translating enzymes crucial in methanogenic metabolic pathways, laid the foundation for the burgeoning field of genetic code expansion. Our primary focus is the discussion of how to successfully engineer the PylRS to recognize new substrates and exhibit higher <i>in vivo</i> activity. We have compiled a comprehensive list of ncAAs incorporable with the PylRS system. Additionally, we also summarize recent successful applications of the PylRS system in creating innovative therapeutic solutions, such as new antibody–drug conjugates, advancements in vaccine modalities, and the potential production of new antimicrobials.","PeriodicalId":32,"journal":{"name":"Chemical Reviews","volume":null,"pages":null},"PeriodicalIF":51.4000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evolution of Pyrrolysyl-tRNA Synthetase: From Methanogenesis to Genetic Code Expansion\",\"authors\":\"Nikolaj G. Koch, Nediljko Budisa\",\"doi\":\"10.1021/acs.chemrev.4c00031\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Over 20 years ago, the pyrrolysine encoding translation system was discovered in specific archaea. Our Review provides an overview of how the once obscure pyrrolysyl-tRNA synthetase (PylRS) tRNA pair, originally responsible for accurately translating enzymes crucial in methanogenic metabolic pathways, laid the foundation for the burgeoning field of genetic code expansion. Our primary focus is the discussion of how to successfully engineer the PylRS to recognize new substrates and exhibit higher <i>in vivo</i> activity. We have compiled a comprehensive list of ncAAs incorporable with the PylRS system. Additionally, we also summarize recent successful applications of the PylRS system in creating innovative therapeutic solutions, such as new antibody–drug conjugates, advancements in vaccine modalities, and the potential production of new antimicrobials.\",\"PeriodicalId\":32,\"journal\":{\"name\":\"Chemical Reviews\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":51.4000,\"publicationDate\":\"2024-07-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemical Reviews\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.chemrev.4c00031\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Reviews","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.chemrev.4c00031","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Evolution of Pyrrolysyl-tRNA Synthetase: From Methanogenesis to Genetic Code Expansion
Over 20 years ago, the pyrrolysine encoding translation system was discovered in specific archaea. Our Review provides an overview of how the once obscure pyrrolysyl-tRNA synthetase (PylRS) tRNA pair, originally responsible for accurately translating enzymes crucial in methanogenic metabolic pathways, laid the foundation for the burgeoning field of genetic code expansion. Our primary focus is the discussion of how to successfully engineer the PylRS to recognize new substrates and exhibit higher in vivo activity. We have compiled a comprehensive list of ncAAs incorporable with the PylRS system. Additionally, we also summarize recent successful applications of the PylRS system in creating innovative therapeutic solutions, such as new antibody–drug conjugates, advancements in vaccine modalities, and the potential production of new antimicrobials.
期刊介绍:
Chemical Reviews is a highly regarded and highest-ranked journal covering the general topic of chemistry. Its mission is to provide comprehensive, authoritative, critical, and readable reviews of important recent research in organic, inorganic, physical, analytical, theoretical, and biological chemistry.
Since 1985, Chemical Reviews has also published periodic thematic issues that focus on a single theme or direction of emerging research.