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Open AccessConcept Paper

The Role of Orthogonality in Genetic Code Expansion

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
Systems Biology Institute, Yale University, West Haven, CT 06516, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 20 June 2019 / Revised: 1 July 2019 / Accepted: 1 July 2019 / Published: 5 July 2019
(This article belongs to the Special Issue Modelling Life-Like Behavior in Systems Chemistry)
PDF [2206 KB, uploaded 5 July 2019]
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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. View Full-Text
Keywords: genetic code expansion; translation; nonstandard amino acids; genome recoding; ribosome engineering; orthogonality; protein engineering genetic code expansion; translation; nonstandard amino acids; genome recoding; ribosome engineering; orthogonality; protein engineering

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Arranz-Gibert, P.; Patel, J.R.; Isaacs, F.J. The Role of Orthogonality in Genetic Code Expansion. Life 2019, 9, 58.

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