Work

Design of growth-coupled measurements of orthogonal aminoacyl-tRNA synthetase function

Year: 2024

Type: article

Abstract: Engineering highly selective orthogonal aminoacyl-tRNA synthetase (aaRS) variants for non-canonical amino acid (ncAAs) incorporation into proteins has proven extremely challenging but is vitally important as many of the most impactful applications of ncAAs are intolerant of heterogeneity in the protein sequence and thus require near perfect incorporation efficiency and substrate selectivity, e.g., the development of novel catalytic sites and biologics. We propose using an established, automated workcell for high-throughput fitness landscape measurement developed by collaborators at NIST, to generate an open-source, global genotype-phenotype map spanning all residues in the Methanocaldococcus jannaschii tyrosyl-tRNA synthetase, one of the most widely used tools for genetic code expansion and chemical biology.

Source: Zenodo (CERN European Organization for Nuclear Research)

Authors: Kelly, Peter, Cortade, Dana, Ross, David, Thyer, Ross

Institutions: The Align Foundation, National Institute of Standards and Technology, Rice University

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

OpenAlex ID: W6930433521

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