Hijacking Translation Initiation for Synthetic Biology. (2nd March 2020)

• Record Type: Journal Article
• Authors: Tharp, Jeffery M.; Krahn, Natalie; Varshney, Umesh; Söll, Dieter
• Is Part Of: Chembiochem. Volume 21:Number 10(2020)
• Page Start: 1387
• Page End: 1396
• Publication Date: 2020-03-02
• Subjects: chemical biology -- genetic code expansion -- noncanonical amino acids -- synthetic biology -- translation initiation; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202000017
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Genetic code expansion (GCE) has revolutionized the field of protein chemistry. Over the past several decades more than 150 different noncanonical amino acids (ncAAs) have been co‐translationally installed into proteins within various host organisms. The vast majority of these ncAAs have been incorporated between the start and stop codons within an open reading frame. This requires that the ncAA be able to form a peptide bond at the α‐amine, limiting the types of molecules that can be genetically encoded. In contrast, the α‐amine of the initiating amino acid is not required for peptide bond formation. Therefore, including the initiator position in GCE allows for co‐translational insertion of more diverse molecules that are modified, or completely lacking an α‐amine. This review explores various methods which have been used to initiate protein synthesis with diverse molecules both in vitro and in vivo. Abstract : Taking control ! Translation initiation can be engineered to occur at any non‐AUG codon using several different strategies both in vitro and in vivo. The α‐amine of the initiating amino acid is not required for elongation which allows for a diverse range of molecules to be incorporated.