Gene

Function (biology)

Amino acid

Biology

Messenger RNA

Transfer RNA

Aminoacylation

Mutation

Biochemistry

Genetic code

Computer science

Computational biology

Translation (biology)

Genetics

Mutagenesis

Synthetic biology

Since the establishment of site-specific mutagenesis of single amino acids to interrogate protein function in the 1970s, biochemists have sought to tailor protein structure in the native cell environment. Fine-tuning the chemical properties of proteins is an indispensable way to address fundamental mechanistic questions. Unnatural amino acids (UAAs) offer the possibility to expand beyond the 20 naturally occurring amino acids in most species and install new and useful chemical functions. Here, we review the literature about advances in UAA incorporation technology from chemoenzymatic aminoacylation of modified tRNAs to in vitro translation systems to genetic encoding of UAAs in the native cell environment and whole organisms. We discuss innovative applications of the UAA technology to challenges in bioengineering and medicine.

Genetic Code Expansion: A Brief History and Perspective