Expansion of the Genetic Code Via Expansion of the Genetic Alphabet
Overview
Affiliations
Current methods to expand the genetic code enable site-specific incorporation of non-canonical amino acids (ncAAs) into proteins in eukaryotic and prokaryotic cells. However, current methods are limited by the number of codons possible, their orthogonality, and possibly their effects on protein synthesis and folding. An alternative approach relies on unnatural base pairs to create a virtually unlimited number of genuinely new codons that are efficiently translated and highly orthogonal because they direct ncAA incorporation using forces other than the complementary hydrogen bonds employed by their natural counterparts. This review outlines progress and achievements made towards developing a functional unnatural base pair and its use to generate semi-synthetic organisms with an expanded genetic alphabet that serves as the basis of an expanded genetic code.
Genetic Code Expansion: Recent Developments and Emerging Applications.
Huang Y, Zhang P, Wang H, Chen Y, Liu T, Luo X Chem Rev. 2024; 125(2):523-598.
PMID: 39737807 PMC: 11758808. DOI: 10.1021/acs.chemrev.4c00216.
Xenobiology for the Biocontainment of Synthetic Organisms: Opportunities and Challenges.
Gomez-Tatay L, Hernandez-Andreu J Life (Basel). 2024; 14(8).
PMID: 39202738 PMC: 11355180. DOI: 10.3390/life14080996.
Engineered Proteins and Materials Utilizing Residue-Specific Noncanonical Amino Acid Incorporation.
Majekodunmi T, Britton D, Montclare J Chem Rev. 2024; 124(15):9113-9135.
PMID: 39008623 PMC: 11327963. DOI: 10.1021/acs.chemrev.3c00855.
A microbiological system for screening the interference of XNA monomers with DNA and RNA metabolism.
Blanchard A, Abramov M, Hassan C, Marliere P, Herdewijn P, Pezo V RSC Adv. 2023; 13(43):29862-29865.
PMID: 37842681 PMC: 10568403. DOI: 10.1039/d3ra06172h.
Extensive breaking of genetic code degeneracy with non-canonical amino acids.
McFeely C, Shakya B, Makovsky C, Haney A, Cropp T, Hartman M Nat Commun. 2023; 14(1):5008.
PMID: 37591858 PMC: 10435567. DOI: 10.1038/s41467-023-40529-x.