Engineering Pyrrolysine Systems for Genetic Code Expansion and Reprogramming.
Chem Rev
; 2024 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-39235427
ABSTRACT
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 synthetase (PylRS)/tRNAPyl pairs. Here we summarize the discovery of the pyrrolysine system and describe the unique properties of PylRS/tRNAPyl pairs that provide a foundation for their transformational role in genetic code expansion and reprogramming. We describe the development of genetic code expansion, from E. coli to all domains of life, using PylRS/tRNAPyl pairs, and the development of systems that biosynthesize and incorporate ncAAs using pyl systems. We review applications that have been uniquely enabled by the development of PylRS/tRNAPyl pairs for incorporating new noncanonical amino acids (ncAAs), and strategies for engineering PylRS/tRNAPyl pairs to add noncanonical monomers, beyond α-L-amino acids, to the genetic code of living organisms. We review rapid progress in the discovery and scalable generation of mutually orthogonal PylRS/tRNAPyl pairs that can be directed to incorporate diverse ncAAs in response to diverse codons, and we review strategies for incorporating multiple distinct ncAAs into proteins using mutually orthogonal PylRS/tRNAPyl pairs. Finally, we review recent advances in the encoded cellular synthesis of noncanonical polymers and macrocycles and discuss future developments for PylRS/tRNAPyl pairs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Chem Rev
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido