Over 20 years ago, the pyrrolysine encoding translation system was discovered in specific
archaea. Our Review provides an overview of how the once obscure pyrrolysyl-tRNA …

Over 500 natural and synthetic amino acids have been genetically encoded in the last two
decades. Incorporating these noncanonical amino acids into proteins enables many …

It is widely hypothesized that removing cellular transfer RNAs (tRNAs)—making their
cognate codons unreadable—might create a genetic firewall to viral infection and enable …

Over the past 16 years, genetic code expansion and reprogramming in living organisms has
been transformed by advances that leverage the unique properties of pyrrolysyl-tRNA …

Our understanding of the complex molecular processes of living organisms at the molecular
level is growing exponentially. This knowledge, together with a powerful arsenal of tools for …

Directed evolution of orthogonal aminoacyl-tRNA synthetases (AARSs) enables site-specific
installation of noncanonical amino acids (ncAAs) into proteins. Traditional evolution …

The direct genetically encoded cell-based synthesis of non-natural peptide and
depsipeptide macrocycles is an outstanding challenge. Here we programme the encoded …

Site-specific incorporation of unnatural amino acids (Uaas) in living cells relies on
engineered aminoacyl-transfer RNA synthetase–tRNA pairs borrowed from a distant domain …

Post-translational modifications (PTM) decorate proteins to provide functional heterogeneity
to an existing proteome. The large number of known PTMs highlights the many ways that …

Transfer RNAs (tRNAs) have a crucial role in protein synthesis, and in recent years, their
therapeutic potential for the treatment of genetic diseases—primarily those associated with a …