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Review
. 2023 Feb;32(2):e4559.
doi: 10.1002/pro.4559.

"Not-so-popular" orthogonal pairs in genetic code expansion

Joseph Andrews  1 , Qinglei Gan  1 , Chenguang Fan  1   2
Affiliations
Review

"Not-so-popular" orthogonal pairs in genetic code expansion

Joseph Andrews et al. Protein Sci. 2023 Feb.

Abstract

During the past decade, genetic code expansion has been proved to be a powerful tool for protein studies and engineering. As the key part, a series of orthogonal pairs have been developed to site-specifically incorporate hundreds of noncanonical amino acids (ncAAs) into proteins by using bacteria, yeast, mammalian cells, animals, or plants as hosts. Among them, the pair of tyrosyl-tRNA synthetase/tRNATyr from Methanococcus jannaschii and the pair of pyrrolysyl-tRNA synthetase/tRNAPyl from Methanosarcina species are the most popular ones. Recently, other "not-so-popular" orthogonal pairs have started to attract attentions, because they can provide more choices of ncAA candidates and are necessary for simultaneous incorporation of multiple ncAAs into a single protein. Here, we summarize the development and applications of those "not-so-popular" orthogonal pairs, providing guidance for studying and engineering proteins.

Keywords: aminoacyl-tRNA synthetases; genetic code expansion; noncanonical amino acids; orthogonal translation systems; tRNA.

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Conflict of interest statement

All authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
NcAAs which have been incorporated by orthogonal pairs derived from TrpRS/tRNATrp
FIGURE 2
FIGURE 2
NcAAs which have been incorporated by orthogonal pairs derived from PheRS/tRNAPhe
FIGURE 3
FIGURE 3
NcAAs which have been incorporated by orthogonal pairs derived from (a) LeuRS/tRNALeu; (b) LysRS/tRNALys; and (c) SepRS/tRNASep
FIGURE 4
FIGURE 4
Mutual orthogonality between selected pairs for (a) ncAAs and (b) tRNAs
See this image and copyright information in PMC

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