Discovering functional, non-proteinogenic amino acid containing, peptides using genetic code reprogramming.
The protein synthesis machinery of the cell, the ribosome and associated factors, is able to accurately follow the canonical genetic code, that which maps RNA sequence to protein sequence, to assemble functional proteins from the twenty or so proteinogenic amino acids. A number of innovative methods have arisen to take advantage of this accurate, and efficient, machinery to direct the assembly of non-proteinogenic amino acids. We review and compare these routes to 'reprogram the genetic code' including in vitro translation, engineered aminoacyl tRNA synthetases, and RNA 'flexizymes'. These studies show that the ribosome is highly tolerant of unnatural amino acids, with hundreds of unusual substrates of varying structure and chemistries being incorporated into protein chains. We also discuss how these methods have been coupled to selection techniques, such as phage display and mRNA display, opening up an exciting new avenue for the production of proteins and peptides with properties and functions beyond that which is possible using proteins composed entirely of the proteinogenic amino acids.
Department of Chemistry, The University of Tokyo, Graduate School of Science, Tokyo, Japan. hsuga@chem.s.u-tokyo.ac.jp.
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JM
Rogers
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Suga
D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005815:Genetic Code; D005818:Genetic Engineering; D015394:Molecular Structure; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D016337:RNA, Catalytic / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D019151:Peptide Library; D010455:Peptides; D016337:RNA, Catalytic; D000604:Amino Acyl-tRNA Synthetases