title: Pyrrolysyl-tRNA synthetase: an ordinary enzyme but an outstanding genetic code expansion tool.
abstract: The genetic incorporation of the 22nd proteinogenic amino acid, pyrrolysine (Pyl) at amber codon is achieved by the action of pyrrolysyl-tRNA synthetase (PylRS) together with its cognate tRNA(Pyl). Unlike most aminoacyl-tRNA synthetases, PylRS displays high substrate side chain promiscuity, low selectivity toward its substrate α-amine, and low selectivity toward the anticodon of tRNA(Pyl). These unique but ordinary features of PylRS as an aminoacyl-tRNA synthetase allow the Pyl incorporation machinery to be easily engineered for the genetic incorporation of more than 100 non-canonical amino acids (NCAAs) or α-hydroxy acids into proteins at amber codon and the reassignment of other codons such as ochre UAA, opal UGA, and four-base AGGA codons to code NCAAs.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77845, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wan
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77845, USA.
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Tharp
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77845, USA. Electronic address: wliu@chem.tamu.edu.
authors.forename: Wenshe R
authors.initials: WR
authors.lastname: Liu
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics* / Q000378:metabolism; D018388:Codon, Terminator; D005815:Genetic Code; D005818:Genetic Engineering / Q000379:methods*; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008697:Methane / Q000378:metabolism; D017020:Methanosarcina / Q000235:genetics* / Q000378:metabolism; D008744:Methylamines / Q000378:metabolism; D008958:Models, Molecular; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D018388:Codon, Terminator; D008744:Methylamines; D012343:RNA, Transfer; C027451:methylamine; D000604:Amino Acyl-tRNA Synthetases; C456839:pyrrolysine; D008239:Lysine; D008697:Methane
keywords: Amber codon; Genetic code expansion; Hydroxy acids; Non-canonical amino acids; Pyrrolysine