Expanding the genetic code

Annu Rev Biophys Biomol Struct. 2006;35:225-49. doi: 10.1146/annurev.biophys.35.101105.121507.


Recently, a general method was developed that makes it possible to genetically encode unnatural amino acids with diverse physical, chemical, or biological properties in Escherichia coli, yeast, and mammalian cells. More than 30 unnatural amino acids have been incorporated into proteins with high fidelity and efficiency by means of a unique codon and corresponding tRNA/aminoacyl-tRNA synthetase pair. These include fluorescent, glycosylated, metal-ion-binding, and redox-active amino acids, as well as amino acids with unique chemical and photochemical reactivity. This methodology provides a powerful tool both for exploring protein structure and function in vitro and in vivo and for generating proteins with new or enhanced properties.

Publication types

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

MeSH terms

  • Amino Acid Substitution
  • Amino Acids / chemistry
  • Amino Acids / genetics
  • Animals
  • Directed Molecular Evolution / methods*
  • Evolution, Molecular*
  • Genetic Code / genetics*
  • Humans
  • Mutagenesis, Site-Directed / methods*
  • Mutation
  • Protein Engineering / methods*
  • Proteins / chemistry*
  • Proteins / genetics*
  • Structure-Activity Relationship


  • Amino Acids
  • Proteins