TY - JOUR
T1 - Engineering of the genetic code
AU - Cohen, Yael
AU - Alfonta, Lital
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2025/2/1
Y1 - 2025/2/1
N2 - The genetic code is a universally conserved mechanism that translates genetic information into proteins, consisting of 64 codons formed by four nucleotide bases. With a few exceptions, the genetic code universally encodes 20 canonical amino acids (AAs) and three stop signals, with many AAs represented by multiple codons. Genetic engineering has expanded this system through approaches like codon reassignment and synthetic base pair introduction, allowing for the incorporation of noncanonical AAs (ncAAs) into proteins, known as genetic code expansion (GCE). These ncAAs add novel functionalities, such as bio-orthogonal handles, fluorophores, and redox-active ncAAs, enhancing the diversity of proteins. Recent advancements include genome-wide recoding, evolution of orthogonal translation components, and synthetic genetic alphabet, with a focus on improving translational efficiency and reducing off-target effects. This review emphasizes strategies for modifying nucleotides, reassessing codons, and engineering translational enzymes, highlighting innovations that tackle challenges in GCE and promote new protein chemistries and biotechnological applications.
AB - The genetic code is a universally conserved mechanism that translates genetic information into proteins, consisting of 64 codons formed by four nucleotide bases. With a few exceptions, the genetic code universally encodes 20 canonical amino acids (AAs) and three stop signals, with many AAs represented by multiple codons. Genetic engineering has expanded this system through approaches like codon reassignment and synthetic base pair introduction, allowing for the incorporation of noncanonical AAs (ncAAs) into proteins, known as genetic code expansion (GCE). These ncAAs add novel functionalities, such as bio-orthogonal handles, fluorophores, and redox-active ncAAs, enhancing the diversity of proteins. Recent advancements include genome-wide recoding, evolution of orthogonal translation components, and synthetic genetic alphabet, with a focus on improving translational efficiency and reducing off-target effects. This review emphasizes strategies for modifying nucleotides, reassessing codons, and engineering translational enzymes, highlighting innovations that tackle challenges in GCE and promote new protein chemistries and biotechnological applications.
UR - http://www.scopus.com/inward/record.url?scp=85213244706&partnerID=8YFLogxK
U2 - 10.1016/j.copbio.2024.103245
DO - 10.1016/j.copbio.2024.103245
M3 - Review article
C2 - 39733656
AN - SCOPUS:85213244706
SN - 0958-1669
VL - 91
JO - Current Opinion in Biotechnology
JF - Current Opinion in Biotechnology
M1 - 103245
ER -