The Role of Orthogonality in Genetic Code Expansion

The genetic code defines how information in the genome is translated into protein. Aside from a handful of isolated exceptions, this code is universal. Researchers have developed techniques to artificially expand the genetic code, repurposing codons and translational machinery to incorporate nonstan...

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Main Authors: Pol Arranz-Gibert, Jaymin R. Patel, Farren J. Isaacs
Format: Article
Language:English
Published: MDPI AG 2019-07-01
Series:Life
Subjects:
Online Access:https://www.mdpi.com/2075-1729/9/3/58
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author Pol Arranz-Gibert
Jaymin R. Patel
Farren J. Isaacs
author_facet Pol Arranz-Gibert
Jaymin R. Patel
Farren J. Isaacs
author_sort Pol Arranz-Gibert
collection DOAJ
description The genetic code defines how information in the genome is translated into protein. Aside from a handful of isolated exceptions, this code is universal. Researchers have developed techniques to artificially expand the genetic code, repurposing codons and translational machinery to incorporate nonstandard amino acids (nsAAs) into proteins. A key challenge for robust genetic code expansion is orthogonality; the engineered machinery used to introduce nsAAs into proteins must co-exist with native translation and gene expression without cross-reactivity or pleiotropy. The issue of orthogonality manifests at several levels, including those of codons, ribosomes, aminoacyl-tRNA synthetases, tRNAs, and elongation factors. In this concept paper, we describe advances in genome recoding, translational engineering and associated challenges rooted in establishing orthogonality needed to expand the genetic code.
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spelling doaj.art-4c349b84aca0436d9ea8c6562e169db62022-12-22T02:22:09ZengMDPI AGLife2075-17292019-07-01935810.3390/life9030058life9030058The Role of Orthogonality in Genetic Code ExpansionPol Arranz-Gibert0Jaymin R. Patel1Farren J. Isaacs2Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USADepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USADepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USAThe genetic code defines how information in the genome is translated into protein. Aside from a handful of isolated exceptions, this code is universal. Researchers have developed techniques to artificially expand the genetic code, repurposing codons and translational machinery to incorporate nonstandard amino acids (nsAAs) into proteins. A key challenge for robust genetic code expansion is orthogonality; the engineered machinery used to introduce nsAAs into proteins must co-exist with native translation and gene expression without cross-reactivity or pleiotropy. The issue of orthogonality manifests at several levels, including those of codons, ribosomes, aminoacyl-tRNA synthetases, tRNAs, and elongation factors. In this concept paper, we describe advances in genome recoding, translational engineering and associated challenges rooted in establishing orthogonality needed to expand the genetic code.https://www.mdpi.com/2075-1729/9/3/58genetic code expansiontranslationnonstandard amino acidsgenome recodingribosome engineeringorthogonalityprotein engineering
spellingShingle Pol Arranz-Gibert
Jaymin R. Patel
Farren J. Isaacs
The Role of Orthogonality in Genetic Code Expansion
Life
genetic code expansion
translation
nonstandard amino acids
genome recoding
ribosome engineering
orthogonality
protein engineering
title The Role of Orthogonality in Genetic Code Expansion
title_full The Role of Orthogonality in Genetic Code Expansion
title_fullStr The Role of Orthogonality in Genetic Code Expansion
title_full_unstemmed The Role of Orthogonality in Genetic Code Expansion
title_short The Role of Orthogonality in Genetic Code Expansion
title_sort role of orthogonality in genetic code expansion
topic genetic code expansion
translation
nonstandard amino acids
genome recoding
ribosome engineering
orthogonality
protein engineering
url https://www.mdpi.com/2075-1729/9/3/58
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