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工程核糖体机械以实现非典型氨基酸掺入。

Engineering Ribosomal Machinery for Noncanonical Amino Acid Incorporation.

机构信息

Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, United States.

出版信息

Chem Rev. 2024 Jun 26;124(12):7712-7730. doi: 10.1021/acs.chemrev.3c00912. Epub 2024 Jun 3.

Abstract

The introduction of noncanonical amino acids into proteins has enabled researchers to modify fundamental physicochemical and functional properties of proteins. While the alteration of the genetic code, via the introduction of orthogonal aminoacyl-tRNA synthetase:tRNA pairs, has driven many of these efforts, the various components involved in the process of translation are important for the development of new genetic codes. In this review, we will focus on recent advances in engineering ribosomal machinery for noncanonical amino acid incorporation and genetic code modification. The engineering of the ribosome itself will be considered, as well as the many factors that interact closely with the ribosome, including both tRNAs and accessory factors, such as the all-important EF-Tu. Given the success of genome re-engineering efforts, future paths for radical alterations of the genetic code will require more expansive alterations in the translation machinery.

摘要

非典型氨基酸的引入使研究人员能够改变蛋白质的基本理化和功能特性。虽然通过引入正交氨酰-tRNA 合成酶:tRNA 对来改变遗传密码推动了这些努力中的许多努力,但翻译过程中涉及的各种成分对于开发新的遗传密码至关重要。在这篇综述中,我们将重点介绍用于非典型氨基酸掺入和遗传密码修饰的核糖体工程的最新进展。将考虑核糖体本身的工程改造,以及与核糖体密切相互作用的许多因素,包括 tRNA 和辅助因子,如非常重要的 EF-Tu。鉴于基因组重新设计工作的成功,遗传密码的激进改变的未来路径将需要对翻译机制进行更广泛的改变。

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