Upgrading aminoacyl-tRNA synthetases for genetic code expansion

Curr Opin Chem Biol. 2018 Oct:46:115-122. doi: 10.1016/j.cbpa.2018.07.014. Epub 2018 Jul 27.

Abstract

Synthesis of proteins with non-canonical amino acids via genetic code expansion is at the forefront of synthetic biology. Progress in this field has enabled site-specific incorporation of over 200 chemically and structurally diverse amino acids into proteins in an increasing number of organisms. This has been facilitated by our ability to repurpose aminoacyl-tRNA synthetases to attach non-canonical amino acids to engineered tRNAs. Current efforts in the field focus on overcoming existing limitations to the simultaneous incorporation of multiple non-canonical amino acids or amino acids that differ from the l-α-amino acid structure (e.g. d-amino acid or β-amino acid). Here, we summarize the progress and challenges in developing more selective and efficient aminoacyl-tRNA synthetases for genetic code expansion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / genetics
  • Amino Acids / metabolism
  • Amino Acyl-tRNA Synthetases / genetics
  • Amino Acyl-tRNA Synthetases / metabolism*
  • Animals
  • Genetic Code*
  • Genetic Engineering / methods*
  • Humans
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism
  • Substrate Specificity
  • Synthetic Biology / methods

Substances

  • Amino Acids
  • RNA, Transfer
  • Amino Acyl-tRNA Synthetases