Breaking the Degeneracy of Sense Codons – How Far Can We Go?

IF 2.3 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Clark A. Jones, Matthew C. T. Hartman
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引用次数: 0

Abstract

Genetic code expansion aims to incorporate non-canonical amino acids (ncAAs) into biological systems, enhancing protein functionality or enabling the in vitro selection of peptides from diverse mRNA displayed libraries. Typically, genetic code expansion has involved reassignment of stop codons to ncAAs through orthogonal translation systems. This review instead focuses on efforts to expand the genetic code by breaking the redundancy of sense codons in vitro and in vivo. In vivo, orthogonal aminoacyl-tRNA synthetase (AARS)/tRNA/AA systems are able to compete with endogenous machinery, enabling partial to full codon reassignment. Recent approaches, like genome recoding, offer potential solutions to reduce competition. In vitro studies utilize cell extract-based or reconstituted translation systems, allowing precise control of codon usage via gene design and tRNA addition, making breaking of sense degeneracy easier. In these systems several unsplit codon boxes have been successfully reassigned multiple to ncAAs. These efforts showcase both the successes and challenges in achieving orthogonality and selective codon decoding and point towards a future where the 64 codons can encode more than 30 monomers, enabling new advances in synthetic biology and drug discovery.

Abstract Image

打破感性密码子的畸变--我们能走多远?
遗传密码扩增的目的是将非规范氨基酸(ncAAs)纳入生物系统,从而增强蛋白质的功能,或从不同的 mRNA 显示文库中体外选择肽。通常情况下,遗传密码扩展涉及通过正交翻译系统将终止密码子重新分配给 ncAAs。本综述则侧重于通过打破体外和体内有义密码子的冗余来扩展遗传密码。在体内,正交的氨基酰-tRNA 合成酶(AARS)/tRNA/AA 系统能够与内源机器竞争,实现部分到全部密码子的重新配置。基因组重编码等最新方法为减少竞争提供了潜在的解决方案。体外研究利用基于细胞提取物的翻译系统或重组翻译系统,通过基因设计和添加 tRNA 来精确控制密码子的使用,从而更容易打破意义退化。在这些系统中,一些未分割的密码子框已成功地重新配置为多个 ncAA。这些努力展示了在实现正交性和选择性密码子解码方面的成功与挑战,并指向未来,64 个密码子可以编码 30 多个单体,从而实现合成生物学和药物发现的新进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Israel Journal of Chemistry
Israel Journal of Chemistry 化学-化学综合
CiteScore
6.20
自引率
0.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: The fledgling State of Israel began to publish its scientific activity in 1951 under the general heading of Bulletin of the Research Council of Israel, which quickly split into sections to accommodate various fields in the growing academic community. In 1963, the Bulletin ceased publication and independent journals were born, with Section A becoming the new Israel Journal of Chemistry. The Israel Journal of Chemistry is the official journal of the Israel Chemical Society. Effective from Volume 50 (2010) it is published by Wiley-VCH. The Israel Journal of Chemistry is an international and peer-reviewed publication forum for Special Issues on timely research topics in all fields of chemistry: from biochemistry through organic and inorganic chemistry to polymer, physical and theoretical chemistry, including all interdisciplinary topics. Each topical issue is edited by one or several Guest Editors and primarily contains invited Review articles. Communications and Full Papers may be published occasionally, if they fit with the quality standards of the journal. The publication language is English and the journal is published twelve times a year.
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