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Selection and validation of orthogonal tRNA/synthetase pairs for the encoding of unnatural amino acids across kingdoms
Book chapter   Peer reviewed

Selection and validation of orthogonal tRNA/synthetase pairs for the encoding of unnatural amino acids across kingdoms

Grace D Galles, Daniel T Infield, Ryan A Mehl and Christopher A Ahern
Ion Channels: Channel Chemical Biology, Engineering, and Physiological Function, Vol.654, pp.3-18
Methods in enzymology, 654, Elsevier
01/01/2021
DOI: 10.1016/bs.mie.2021.03.009
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC12758591/View
Open Access

Abstract

As an increasing number of protein structures are resolved at atomic and near-atomic resolution, conventional amino acid mutagenesis may be insufficient to test many mechanistic hypotheses. As a result, the development of new tRNA/aminoacyl-tRNA synthetase (aaRS) pairs has become an important tool for determining intricate molecular interactions and understanding protein structures. This chapter describes in detail the directed evolution of new tRNA/aaRS pairs in Escherichia coli for the incorporation of non-canonical amino acids (ncAA). Section 1 describes the selection of new tRNA/aaRS pairs in E. coli. Section 2 details the use of a synthetase to incorporate an ncAA into a mammalian cell line, and 1 Introduction, 2 Screening of the pyrrolysine synthetase library in both include methods on the determination of synthetase efficacy and fidelity.

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