Engineering Ribosomal Machinery for Noncanonical Amino Acid Incorporation

• Published in: Chemical reviews Vol. 124; no. 12; pp. 7712 - 7730
• Main Authors: Ishida, Satoshi, Ngo, Phuoc H. T., Gundlach, Arno, Ellington, Andrew
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 26.06.2024
• Subjects: Amino acids; Amino Acids - chemistry; Amino Acids - metabolism; Amino Acyl-tRNA Synthetases - genetics; Amino Acyl-tRNA Synthetases - metabolism; Genetic Code; Protein Biosynthesis; Protein Engineering; Proteins; Ribosomes - metabolism; RNA, Transfer - chemistry; RNA, Transfer - genetics; RNA, Transfer - metabolism
• ISSN: 0009-2665; 1520-6890; 1520-6890
• DOI: 10.1021/acs.chemrev.3c00912

The introduction of noncanonical amino acids into proteins has enabled researchers to modify fundamental physicochemical and functional properties of proteins. While the alteration of the genetic code, via the introduction of orthogonal aminoacyl-tRNA synthetase:tRNA pairs, has driven many of these efforts, the various components involved in the process of translation are important for the development of new genetic codes. In this review, we will focus on recent advances in engineering ribosomal machinery for noncanonical amino acid incorporation and genetic code modification. The engineering of the ribosome itself will be considered, as well as the many factors that interact closely with the ribosome, including both tRNAs and accessory factors, such as the all-important EF-Tu. Given the success of genome re-engineering efforts, future paths for radical alterations of the genetic code will require more expansive alterations in the translation machinery.