Continuous directed evolution of aminoacyl-tRNA synthetases View Full Text


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Article Info

DATE

2017-12

AUTHORS

David I Bryson, Chenguang Fan, Li-Tao Guo, Corwin Miller, Dieter Söll, David R Liu

ABSTRACT

Directed evolution of orthogonal aminoacyl-tRNA synthetases (AARSs) enables site-specific installation of noncanonical amino acids (ncAAs) into proteins. Traditional evolution techniques typically produce AARSs with greatly reduced activity and selectivity compared to their wild-type counterparts. We designed phage-assisted continuous evolution (PACE) selections to rapidly produce highly active and selective orthogonal AARSs through hundreds of generations of evolution. PACE of a chimeric Methanosarcina spp. pyrrolysyl-tRNA synthetase (PylRS) improved its enzymatic efficiency (kcat/KMtRNA) 45-fold compared to the parent enzyme. Transplantation of the evolved mutations into other PylRS-derived synthetases improved yields of proteins containing noncanonical residues up to 9.7-fold. Simultaneous positive and negative selection PACE over 48 h greatly improved the selectivity of a promiscuous Methanocaldococcus jannaschii tyrosyl-tRNA synthetase variant for site-specific incorporation of p-iodo-L-phenylalanine. These findings offer new AARSs that increase the utility of orthogonal translation systems and establish the capability of PACE to efficiently evolve orthogonal AARSs with high activity and amino acid specificity. More... »

PAGES

1253

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nchembio.2474

    DOI

    http://dx.doi.org/10.1038/nchembio.2474

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1092234018

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29035361


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    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nchembio.2474'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nchembio.2474'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nchembio.2474'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nchembio.2474'


     

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