title: Experimental challenges of sense codon reassignment: an innovative approach to genetic code expansion.
abstract: The addition of new and versatile chemical and biological properties to proteins pursued through incorporation of non-canonical amino acids is at present primarily achieved by stop codon suppression. However, it is critical to find new "blank" codons to increase the variety and efficiency of such insertions, thereby taking 'sense codon recoding' to center stage in the field of genetic code expansion. Current thought optimistically suggests the use of the pyrrolysine system coupled with re-synthesis of genomic information towards achieving sense codon reassignment. Upon review of the serious experimental challenges reported in recent studies, we propose that success in this area will depend on the re-synthesis of genomes, but also on 'rewiring' the mechanism of protein synthesis and of its quality control.
authors: Synthetic Biology and Bioenergy, J. Craig Venter Institute, Rockville, MD 20850, USA. Electronic address: rkrishna@jcvi.org.
authors: Radha
authors: R
authors: Krishnakumar
authors: Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
authors: Jiqiang
authors: J
authors: Ling
mesh_terms: D000596:Amino Acids / Q000235:genetics*; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics; D003062:Codon / Q000235:genetics*; D018388:Codon, Terminator / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005815:Genetic Code; D014176:Protein Biosynthesis / Q000235:genetics*; D011506:Proteins / Q000235:genetics
chemical_list: D000596:Amino Acids; D003062:Codon; D018388:Codon, Terminator; D011506:Proteins; D000604:Amino Acyl-tRNA Synthetases
keywords: Genetic code expansion; Mycoplasma mycoides; OTS; Pyl; Pyrrolysyl-tRNA synthetase; Sense codon recoding; aaRS; aminoacyl-tRNA synthetase; ncAAs; non-canonical amino acids; orthogonal translation system; pyrrolysine