Engineering Pyrrolysine Systems for Genetic Code Expansion and Reprogramming,Chemical Reviews

当前位置： X-MOL 学术 › Chem. Rev. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Engineering Pyrrolysine Systems for Genetic Code Expansion and Reprogramming
Chemical Reviews ( IF 51.4 ) Pub Date : 2024-09-05 , DOI: 10.1021/acs.chemrev.4c00243
Daniel L Dunkelmann _{1,

2} , Jason W Chin ₁

Affiliation

Over the past 16 years, genetic code expansion and reprogramming in living organisms has been transformed by advances that leverage the unique properties of pyrrolysyl-tRNA synthetase (PylRS)/tRNA^Pyl pairs. Here we summarize the discovery of the pyrrolysine system and describe the unique properties of PylRS/tRNA^Pyl pairs that provide a foundation for their transformational role in genetic code expansion and reprogramming. We describe the development of genetic code expansion, from E. coli to all domains of life, using PylRS/tRNA^Pyl pairs, and the development of systems that biosynthesize and incorporate ncAAs using pyl systems. We review applications that have been uniquely enabled by the development of PylRS/tRNA^Pyl pairs for incorporating new noncanonical amino acids (ncAAs), and strategies for engineering PylRS/tRNA^Pyl pairs to add noncanonical monomers, beyond α-L-amino acids, to the genetic code of living organisms. We review rapid progress in the discovery and scalable generation of mutually orthogonal PylRS/tRNA^Pyl pairs that can be directed to incorporate diverse ncAAs in response to diverse codons, and we review strategies for incorporating multiple distinct ncAAs into proteins using mutually orthogonal PylRS/tRNA^Pyl pairs. Finally, we review recent advances in the encoded cellular synthesis of noncanonical polymers and macrocycles and discuss future developments for PylRS/tRNA^Pyl pairs.

中文翻译：

用于遗传密码扩增和重编程的工程化吡咯赖氨酸系统

在过去的 16 年里，利用吡咯赖氨酰-tRNA 合成酶（PylRS）/tRNA^Pyl 对的独特特性的进步改变了生物体中的遗传密码扩增和重编程。在这里，我们总结了吡咯赖氨酸系统的发现，并描述了 PylRS/tRNA^Pyl 对的独特特性，这些特性为它们在遗传密码扩增和重编程中的转化作用提供了基础。我们描述了使用 PylRS/tRNA^Pyl 对从大肠杆菌到生命所有领域的遗传密码扩展的发展，以及使用 pyl 系统生物合成和掺入 ncAA 的系统的发展。我们回顾了通过开发 PylRS/tRNA^Pyl 对来掺入新的非经典氨基酸（ncAA）而独特实现的应用，以及工程化 PylRS/tRNA^Pyl 对以将非经典单体添加到 α-L-氨基酸之外的策略到生物体的遗传密码中。我们回顾了发现和可扩展生成相互正交的 PylRS/tRNA^Pyl 对的快速进展，这些对可以指导以响应不同的密码子来掺入不同的 ncAA，并且我们回顾了使用相互正交的 PylRS/tRNA^Pyl 对将多个不同的 ncAA 掺入蛋白质的策略。最后，我们回顾了非经典聚合物和大环编码细胞合成的最新进展，并讨论了 PylRS/tRNA^Pyl 对的未来发展。

更新日期：2024-09-05

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南