A designed phenylalanyl-tRNA synthetase variant allows efficient in vivo incorporation of aryl ketone functionality into proteins.
Incorporation of non-natural amino acids into proteins in vivo expands the scope of protein synthesis and design. p-Acetylphenylalanine was incorporated into recombinant dihydrofolate reductase (DHFR) in Escherichia coli via a computationally designed mutant form of the phenylalanyl-tRNA synthetase of the host. DHFR outfitted with ketone functionality can be chemoselectively ligated with hydrazide reagents under mild conditions.
Datta
Deepshikha
D
Division of Chemistry and Chemical Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.
Wang
Pin
P
Carrico
Isaac S
IS
Mayo
Stephen L
SL
Tirrell
David A
DA
D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D007659:Ketones / Q000378:metabolism*; D016296:Mutagenesis; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D010652:Phenylalanine-tRNA Ligase / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*
D007659:Ketones; D011994:Recombinant Proteins; D010649:Phenylalanine; D010652:Phenylalanine-tRNA Ligase