O papel da ortogonalidade na expansão do código genético: mero acaso, fortuita necessidade ou design inteligente?

quinta-feira, outubro 31, 2019

The Role of Orthogonality in Genetic Code Expansion

by Pol Arranz-Gibert 1,2,†,Jaymin R. Patel 1,2,† andFarren J. Isaacs 1,2,*OrcID

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



Abstract

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. 

Keywords: genetic code expansion; translation; nonstandard amino acids; genome recoding; ribosome engineering; orthogonality; protein engineering

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