Aminoacyl-tRNA Synthetases and tRNAs for an Expanded Genetic Code: What Makes Them Orthogonal?

Int J Mol Sci. 2019 Apr 19;20(8):1929. doi: 10.3390/ijms20081929.


In the past two decades, tRNA molecules and their corresponding aminoacyl-tRNA synthetases (aaRS) have been extensively used in synthetic biology to genetically encode post-translationally modified and unnatural amino acids. In this review, we briefly examine one fundamental requirement for the successful application of tRNA/aaRS pairs for expanding the genetic code. This requirement is known as "orthogonality"-the ability of a tRNA and its corresponding aaRS to interact exclusively with each other and avoid cross-reactions with additional types of tRNAs and aaRSs in a given organism.

Keywords: aminoacyl-tRNA synthetases; expanded genetic code; orthogonal translation systems; synthetic biology; tRNA.

Publication types

  • Review

MeSH terms

  • Amino Acyl-tRNA Synthetases / chemistry
  • Amino Acyl-tRNA Synthetases / genetics*
  • Genetic Code*
  • Genetic Engineering
  • RNA, Transfer / chemistry
  • RNA, Transfer / genetics*
  • Synthetic Biology


  • RNA, Transfer
  • Amino Acyl-tRNA Synthetases