tRNA 在遗传密码扩展中的核心作用。
The central role of tRNA in genetic code expansion.
机构信息
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
出版信息
Biochim Biophys Acta Gen Subj. 2017 Nov;1861(11 Pt B):3001-3008. doi: 10.1016/j.bbagen.2017.03.012. Epub 2017 Mar 18.
BACKGROUND
The development of orthogonal translation systems (OTSs) for genetic code expansion (GCE) has allowed for the incorporation of a diverse array of non-canonical amino acids (ncAA) into proteins. Transfer RNA, the central molecule in the translation of the genetic message into proteins, plays a significant role in the efficiency of ncAA incorporation.
SCOPE OF REVIEW
Here we review the biochemical basis of OTSs for genetic code expansion. We focus on the role of tRNA and discuss strategies used to engineer tRNA for the improvement of ncAA incorporation into proteins.
MAJOR CONCLUSIONS
The engineering of orthogonal tRNAs for GCE has significantly improved the incorporation of ncAAs. However, there are numerous unintended consequences of orthogonal tRNA engineering that cannot be predicted ab initio.
GENERAL SIGNIFICANCE
Genetic code expansion has allowed for the incorporation of a great diversity of ncAAs and novel chemistries into proteins, making significant contributions to our understanding of biological molecules and interactions. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue.
背景
正交翻译系统（OTS）的发展为遗传密码扩展（GCE）提供了可能，从而可以将各种非标准氨基酸（ncAA）掺入蛋白质中。转移 RNA 是将遗传信息翻译成蛋白质的中心分子，在 ncAA 掺入的效率中起着重要作用。
综述范围
本文综述了遗传密码扩展的 OTS 的生化基础。我们重点讨论了 tRNA 的作用，并讨论了用于工程化 tRNA 以提高 ncAA 掺入蛋白质的策略。
主要结论
为 GCE 工程设计正交 tRNA 显著提高了 ncAA 的掺入效率。然而，正交 tRNA 工程存在许多无法预先预测的意外后果。
一般意义
遗传密码扩展允许将大量的 ncAA 和新的化学物质掺入蛋白质中，为我们对生物分子和相互作用的理解做出了重大贡献。本文是题为“合成生物学的生物化学-最新进展”的特刊的一部分，客座编辑为 Ilka Heinemann 博士和 Patrick O'Donoghue 博士。
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