tRNA engineering strategies for genetic code expansion

YouJin Kim; Suho Cho; Joo-Chan Kim; Hee-Sung Park

doi:10.3389/fgene.2024.1373250

tRNA engineering strategies for genetic code expansion

Front Genet. 2024 Mar 7:15:1373250. doi: 10.3389/fgene.2024.1373250. eCollection 2024.

Authors

YouJin Kim^#¹, Suho Cho^#¹, Joo-Chan Kim¹, Hee-Sung Park¹

Affiliation

¹ Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.

^# Contributed equally.

Abstract

The advancement of genetic code expansion (GCE) technology is attributed to the establishment of specific aminoacyl-tRNA synthetase/tRNA pairs. While earlier improvements mainly focused on aminoacyl-tRNA synthetases, recent studies have highlighted the importance of optimizing tRNA sequences to enhance both unnatural amino acid incorporation efficiency and orthogonality. Given the crucial role of tRNAs in the translation process and their substantial impact on overall GCE efficiency, ongoing efforts are dedicated to the development of tRNA engineering techniques. This review explores diverse tRNA engineering approaches and provides illustrative examples in the context of GCE, offering insights into the user-friendly implementation of GCE technology.

Keywords: directed evolution; genetic code expansion; rational design; tRNA engineering; unnatural amino acid.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (2023R1A2C1005945).