Continuous directed evolution of aminoacyl-tRNA synthetases View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


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

  • 2004-10. The site-specific incorporation of p-iodo-L-phenylalanine into proteins for structure determination in NATURE BIOTECHNOLOGY
  • 1982-07. Effects of bacteriophage f1 gene III protein on the host cell membrane in MOLECULAR GENETICS AND GENOMICS
  • 2015-12. Development of potent in vivo mutagenesis plasmids with broad mutational spectra in NATURE COMMUNICATIONS
  • 2016-05. Continuous evolution of Bacillus thuringiensis toxins overcomes insect resistance in NATURE
  • 2014-03. Negative selection and stringency modulation in phage-assisted continuous evolution in NATURE CHEMICAL BIOLOGY
  • 2008-04. Genetically encoding Nε-acetyllysine in recombinant proteins in NATURE CHEMICAL BIOLOGY
  • 2009-02. Pyrrolysyl-tRNA synthetase–tRNAPyl structure reveals the molecular basis of orthogonality in NATURE
  • 1998-02. The structural basis of phage display elucidated by the crystal structure of the N-terminal domains of g3p in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2015-10. Continuous directed evolution of DNA-binding proteins to improve TALEN specificity in NATURE METHODS
  • 2011-04. A system for the continuous directed evolution of biomolecules in NATURE
  • 2015-12. Evolution of translation machinery in recoded bacteria enables multi-site incorporation of nonstandard amino acids in NATURE BIOTECHNOLOGY
  • 2013-10. Upgrading protein synthesis for synthetic biology in NATURE CHEMICAL BIOLOGY
  • 2014-12. A system for the continuous directed evolution of proteases rapidly reveals drug-resistance mutations in NATURE COMMUNICATIONS
  • 2009-08. Programming cells by multiplex genome engineering and accelerated evolution in NATURE
  • 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


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Genetics", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Amino Acids", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Amino Acyl-tRNA Synthetases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Biocatalysis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Directed Molecular Evolution", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Methanocaldococcus", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Methanosarcina", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Conformation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proteins", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Harvard University", 
              "id": "https://www.grid.ac/institutes/grid.38142.3c", 
              "name": [
                "Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bryson", 
            "givenName": "David I", 
            "id": "sg:person.01277462612.88", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01277462612.88"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Arkansas at Fayetteville", 
              "id": "https://www.grid.ac/institutes/grid.411017.2", 
              "name": [
                "Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fan", 
            "givenName": "Chenguang", 
            "id": "sg:person.0726402407.07", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0726402407.07"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Yale University", 
              "id": "https://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Guo", 
            "givenName": "Li-Tao", 
            "id": "sg:person.01173314043.56", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01173314043.56"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Yale University", 
              "id": "https://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Miller", 
            "givenName": "Corwin", 
            "id": "sg:person.0670575615.47", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0670575615.47"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Yale University", 
              "id": "https://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.", 
                "Department of Chemistry, Yale University, New Haven, Connecticut, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "S\u00f6ll", 
            "givenName": "Dieter", 
            "id": "sg:person.012067245622.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012067245622.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Broad Institute", 
              "id": "https://www.grid.ac/institutes/grid.66859.34", 
              "name": [
                "Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.", 
                "Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA.", 
                "Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA."
              ], 
              "type": "Organization"
            }, 
            "familyName": "Liu", 
            "givenName": "David R", 
            "id": "sg:person.0654235666.54", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654235666.54"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1073/pnas.0804157105", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000818675"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.3515", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001171659", 
              "https://doi.org/10.1038/nmeth.3515"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0022-2836(05)80265-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001603185"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature08187", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004117037", 
              "https://doi.org/10.1038/nature08187"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature08187", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004117037", 
              "https://doi.org/10.1038/nature08187"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/ja058262u", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005213075"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/ja058262u", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005213075"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.febslet.2007.06.004", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005289941"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.1419737111", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007847065"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.3372", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008029873", 
              "https://doi.org/10.1038/nbt.3372"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.1453", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009252608", 
              "https://doi.org/10.1038/nchembio.1453"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1077464", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009906122"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.jmb.2009.10.030", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010352193"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature17938", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011009109", 
              "https://doi.org/10.1038/nature17938"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1241459", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011644178"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0002387", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013268232"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/ja5069728", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013286517"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt1013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016685894", 
              "https://doi.org/10.1038/nbt1013"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt1013", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016685894", 
              "https://doi.org/10.1038/nbt1013"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/nar/gkv800", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017566530"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature09929", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017568559", 
              "https://doi.org/10.1038/nature09929"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms6352", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018009622", 
              "https://doi.org/10.1038/ncomms6352"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.73", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018517323", 
              "https://doi.org/10.1038/nchembio.73"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0704769104", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019469535"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.febslet.2012.01.029", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021358073"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0022-2836(02)00260-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023347934"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0014-5793(00)01198-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024430074"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.bbapap.2014.03.002", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024562392"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)80342-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026580014"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1146/annurev.biochem.052308.105824", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032969013"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.jmb.2008.02.045", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034884603"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m112.396754", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035619483"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms9425", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037681456", 
              "https://doi.org/10.1038/ncomms9425"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.1339", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038247507", 
              "https://doi.org/10.1038/nchembio.1339"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.molcel.2009.07.027", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038287493"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.chembiol.2008.10.004", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038423096"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/bi3016185", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039406946"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1146/annurev-biochem-060713-035737", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042649778"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0601756103", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044268128"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00331849", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044833631", 
              "https://doi.org/10.1007/bf00331849"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0969-2126(99)80092-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046343057"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/anie.200904035", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047561132"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.79.17.5200", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049618417"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature07611", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050344096", 
              "https://doi.org/10.1038/nature07611"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nsb0298-140", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052877349", 
              "https://doi.org/10.1038/nsb0298-140"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/acschembio.6b00765", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055135344"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/acssynbio.5b00197", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055140769"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/ol300045c", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1056252641"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/jb.175.6.1856-1859.1993", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062722498"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2017-12", 
        "datePublishedReg": "2017-12-01", 
        "description": "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.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/nchembio.2474", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.4897755", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.3867207", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2508989", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.5124751", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.6618309", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.4103606", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1327431", 
            "issn": [
              "1552-4450", 
              "1552-4469"
            ], 
            "name": "Nature Chemical Biology", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "12", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "13"
          }
        ], 
        "name": "Continuous directed evolution of aminoacyl-tRNA synthetases", 
        "pagination": "1253", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "3ed3d323f9901511de581f233240f0148a3a2128b83cbe92a459060a4ec6fb71"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "29035361"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "101231976"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/nchembio.2474"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1092234018"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/nchembio.2474", 
          "https://app.dimensions.ai/details/publication/pub.1092234018"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T12:25", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000362_0000000362/records_87106_00000001.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/nchembio.2474"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    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'


     

    This table displays all metadata directly associated to this object as RDF triples.

    312 TRIPLES      21 PREDICATES      83 URIs      29 LITERALS      17 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/nchembio.2474 schema:about N1be9e909627d47329e0ddea422c10458
    2 N437a17df0a204f88a88e846bef4da477
    3 N56d2361673274909b233743a372887d2
    4 N7e63db6ec39643de89688c7f89be4fdd
    5 N986a4204d2ff442bbdf4f28c50bcfe2d
    6 Nb936ebddcb384e61a9501e7709db27a2
    7 Nc4d8c36ba94f4fd7a3592f58ed33d164
    8 Nd1eed52feec1479da5ecfab2515144e6
    9 anzsrc-for:06
    10 anzsrc-for:0604
    11 schema:author N9361e12cfd134f81940d97500e150117
    12 schema:citation sg:pub.10.1007/bf00331849
    13 sg:pub.10.1038/nature07611
    14 sg:pub.10.1038/nature08187
    15 sg:pub.10.1038/nature09929
    16 sg:pub.10.1038/nature17938
    17 sg:pub.10.1038/nbt.3372
    18 sg:pub.10.1038/nbt1013
    19 sg:pub.10.1038/nchembio.1339
    20 sg:pub.10.1038/nchembio.1453
    21 sg:pub.10.1038/nchembio.73
    22 sg:pub.10.1038/ncomms6352
    23 sg:pub.10.1038/ncomms9425
    24 sg:pub.10.1038/nmeth.3515
    25 sg:pub.10.1038/nsb0298-140
    26 https://doi.org/10.1002/anie.200904035
    27 https://doi.org/10.1016/j.bbapap.2014.03.002
    28 https://doi.org/10.1016/j.chembiol.2008.10.004
    29 https://doi.org/10.1016/j.febslet.2007.06.004
    30 https://doi.org/10.1016/j.febslet.2012.01.029
    31 https://doi.org/10.1016/j.jmb.2008.02.045
    32 https://doi.org/10.1016/j.jmb.2009.10.030
    33 https://doi.org/10.1016/j.molcel.2009.07.027
    34 https://doi.org/10.1016/s0014-5793(00)01198-4
    35 https://doi.org/10.1016/s0022-2836(02)00260-7
    36 https://doi.org/10.1016/s0022-2836(05)80265-7
    37 https://doi.org/10.1016/s0092-8674(00)80342-6
    38 https://doi.org/10.1016/s0969-2126(99)80092-6
    39 https://doi.org/10.1021/acschembio.6b00765
    40 https://doi.org/10.1021/acssynbio.5b00197
    41 https://doi.org/10.1021/bi3016185
    42 https://doi.org/10.1021/ja058262u
    43 https://doi.org/10.1021/ja5069728
    44 https://doi.org/10.1021/ol300045c
    45 https://doi.org/10.1073/pnas.0601756103
    46 https://doi.org/10.1073/pnas.0704769104
    47 https://doi.org/10.1073/pnas.0804157105
    48 https://doi.org/10.1073/pnas.1419737111
    49 https://doi.org/10.1073/pnas.79.17.5200
    50 https://doi.org/10.1074/jbc.m112.396754
    51 https://doi.org/10.1093/nar/gkv800
    52 https://doi.org/10.1126/science.1077464
    53 https://doi.org/10.1126/science.1241459
    54 https://doi.org/10.1128/jb.175.6.1856-1859.1993
    55 https://doi.org/10.1146/annurev-biochem-060713-035737
    56 https://doi.org/10.1146/annurev.biochem.052308.105824
    57 https://doi.org/10.1371/journal.pone.0002387
    58 schema:datePublished 2017-12
    59 schema:datePublishedReg 2017-12-01
    60 schema:description 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 (k<sub>cat</sub>/K<sub>M</sub><sup>tRNA</sup>) 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.
    61 schema:genre research_article
    62 schema:inLanguage en
    63 schema:isAccessibleForFree true
    64 schema:isPartOf N5a7d2741ea5e480e9cfaab56789b4b78
    65 Ne88261c342524b50812866011e2afc72
    66 sg:journal.1327431
    67 schema:name Continuous directed evolution of aminoacyl-tRNA synthetases
    68 schema:pagination 1253
    69 schema:productId N2905e276965444fba2e887854005702b
    70 N5e3aaf1b71ba4564855c48d2b335800d
    71 N633f929364a348e49da0869c956f2f63
    72 N988c652ab1bf4295ba710b9a90d3c05d
    73 Nd8157d9a74a9473cb3d5cd2ca03c5058
    74 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092234018
    75 https://doi.org/10.1038/nchembio.2474
    76 schema:sdDatePublished 2019-04-11T12:25
    77 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    78 schema:sdPublisher N698a46c1c89f4c7f878e53f44e1e001f
    79 schema:url https://www.nature.com/articles/nchembio.2474
    80 sgo:license sg:explorer/license/
    81 sgo:sdDataset articles
    82 rdf:type schema:ScholarlyArticle
    83 N1be9e909627d47329e0ddea422c10458 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    84 schema:name Methanosarcina
    85 rdf:type schema:DefinedTerm
    86 N2905e276965444fba2e887854005702b schema:name readcube_id
    87 schema:value 3ed3d323f9901511de581f233240f0148a3a2128b83cbe92a459060a4ec6fb71
    88 rdf:type schema:PropertyValue
    89 N2c089685defe4b5ca6a4fed427aad3e3 rdf:first sg:person.0726402407.07
    90 rdf:rest N819ef4b4edd94d49b001b5e6d0064c0f
    91 N437a17df0a204f88a88e846bef4da477 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    92 schema:name Amino Acids
    93 rdf:type schema:DefinedTerm
    94 N56d2361673274909b233743a372887d2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    95 schema:name Biocatalysis
    96 rdf:type schema:DefinedTerm
    97 N56e19249f570465bbc367762d5df8d4f rdf:first sg:person.012067245622.45
    98 rdf:rest N7d82aa86428f496290531b95c64ad065
    99 N5a7d2741ea5e480e9cfaab56789b4b78 schema:issueNumber 12
    100 rdf:type schema:PublicationIssue
    101 N5e3aaf1b71ba4564855c48d2b335800d schema:name dimensions_id
    102 schema:value pub.1092234018
    103 rdf:type schema:PropertyValue
    104 N633f929364a348e49da0869c956f2f63 schema:name pubmed_id
    105 schema:value 29035361
    106 rdf:type schema:PropertyValue
    107 N698a46c1c89f4c7f878e53f44e1e001f schema:name Springer Nature - SN SciGraph project
    108 rdf:type schema:Organization
    109 N7d82aa86428f496290531b95c64ad065 rdf:first sg:person.0654235666.54
    110 rdf:rest rdf:nil
    111 N7e63db6ec39643de89688c7f89be4fdd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    112 schema:name Proteins
    113 rdf:type schema:DefinedTerm
    114 N819ef4b4edd94d49b001b5e6d0064c0f rdf:first sg:person.01173314043.56
    115 rdf:rest N91e117ef0df04f10aa06d48b26ff8c3d
    116 N91e117ef0df04f10aa06d48b26ff8c3d rdf:first sg:person.0670575615.47
    117 rdf:rest N56e19249f570465bbc367762d5df8d4f
    118 N9361e12cfd134f81940d97500e150117 rdf:first sg:person.01277462612.88
    119 rdf:rest N2c089685defe4b5ca6a4fed427aad3e3
    120 N986a4204d2ff442bbdf4f28c50bcfe2d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    121 schema:name Methanocaldococcus
    122 rdf:type schema:DefinedTerm
    123 N988c652ab1bf4295ba710b9a90d3c05d schema:name nlm_unique_id
    124 schema:value 101231976
    125 rdf:type schema:PropertyValue
    126 Nb936ebddcb384e61a9501e7709db27a2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    127 schema:name Molecular Conformation
    128 rdf:type schema:DefinedTerm
    129 Nc4d8c36ba94f4fd7a3592f58ed33d164 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    130 schema:name Directed Molecular Evolution
    131 rdf:type schema:DefinedTerm
    132 Nd1eed52feec1479da5ecfab2515144e6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    133 schema:name Amino Acyl-tRNA Synthetases
    134 rdf:type schema:DefinedTerm
    135 Nd8157d9a74a9473cb3d5cd2ca03c5058 schema:name doi
    136 schema:value 10.1038/nchembio.2474
    137 rdf:type schema:PropertyValue
    138 Ne88261c342524b50812866011e2afc72 schema:volumeNumber 13
    139 rdf:type schema:PublicationVolume
    140 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    141 schema:name Biological Sciences
    142 rdf:type schema:DefinedTerm
    143 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
    144 schema:name Genetics
    145 rdf:type schema:DefinedTerm
    146 sg:grant.2508989 http://pending.schema.org/fundedItem sg:pub.10.1038/nchembio.2474
    147 rdf:type schema:MonetaryGrant
    148 sg:grant.3867207 http://pending.schema.org/fundedItem sg:pub.10.1038/nchembio.2474
    149 rdf:type schema:MonetaryGrant
    150 sg:grant.4103606 http://pending.schema.org/fundedItem sg:pub.10.1038/nchembio.2474
    151 rdf:type schema:MonetaryGrant
    152 sg:grant.4897755 http://pending.schema.org/fundedItem sg:pub.10.1038/nchembio.2474
    153 rdf:type schema:MonetaryGrant
    154 sg:grant.5124751 http://pending.schema.org/fundedItem sg:pub.10.1038/nchembio.2474
    155 rdf:type schema:MonetaryGrant
    156 sg:grant.6618309 http://pending.schema.org/fundedItem sg:pub.10.1038/nchembio.2474
    157 rdf:type schema:MonetaryGrant
    158 sg:journal.1327431 schema:issn 1552-4450
    159 1552-4469
    160 schema:name Nature Chemical Biology
    161 rdf:type schema:Periodical
    162 sg:person.01173314043.56 schema:affiliation https://www.grid.ac/institutes/grid.47100.32
    163 schema:familyName Guo
    164 schema:givenName Li-Tao
    165 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01173314043.56
    166 rdf:type schema:Person
    167 sg:person.012067245622.45 schema:affiliation https://www.grid.ac/institutes/grid.47100.32
    168 schema:familyName Söll
    169 schema:givenName Dieter
    170 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012067245622.45
    171 rdf:type schema:Person
    172 sg:person.01277462612.88 schema:affiliation https://www.grid.ac/institutes/grid.38142.3c
    173 schema:familyName Bryson
    174 schema:givenName David I
    175 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01277462612.88
    176 rdf:type schema:Person
    177 sg:person.0654235666.54 schema:affiliation https://www.grid.ac/institutes/grid.66859.34
    178 schema:familyName Liu
    179 schema:givenName David R
    180 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654235666.54
    181 rdf:type schema:Person
    182 sg:person.0670575615.47 schema:affiliation https://www.grid.ac/institutes/grid.47100.32
    183 schema:familyName Miller
    184 schema:givenName Corwin
    185 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0670575615.47
    186 rdf:type schema:Person
    187 sg:person.0726402407.07 schema:affiliation https://www.grid.ac/institutes/grid.411017.2
    188 schema:familyName Fan
    189 schema:givenName Chenguang
    190 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0726402407.07
    191 rdf:type schema:Person
    192 sg:pub.10.1007/bf00331849 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044833631
    193 https://doi.org/10.1007/bf00331849
    194 rdf:type schema:CreativeWork
    195 sg:pub.10.1038/nature07611 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050344096
    196 https://doi.org/10.1038/nature07611
    197 rdf:type schema:CreativeWork
    198 sg:pub.10.1038/nature08187 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004117037
    199 https://doi.org/10.1038/nature08187
    200 rdf:type schema:CreativeWork
    201 sg:pub.10.1038/nature09929 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017568559
    202 https://doi.org/10.1038/nature09929
    203 rdf:type schema:CreativeWork
    204 sg:pub.10.1038/nature17938 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011009109
    205 https://doi.org/10.1038/nature17938
    206 rdf:type schema:CreativeWork
    207 sg:pub.10.1038/nbt.3372 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008029873
    208 https://doi.org/10.1038/nbt.3372
    209 rdf:type schema:CreativeWork
    210 sg:pub.10.1038/nbt1013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016685894
    211 https://doi.org/10.1038/nbt1013
    212 rdf:type schema:CreativeWork
    213 sg:pub.10.1038/nchembio.1339 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038247507
    214 https://doi.org/10.1038/nchembio.1339
    215 rdf:type schema:CreativeWork
    216 sg:pub.10.1038/nchembio.1453 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009252608
    217 https://doi.org/10.1038/nchembio.1453
    218 rdf:type schema:CreativeWork
    219 sg:pub.10.1038/nchembio.73 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018517323
    220 https://doi.org/10.1038/nchembio.73
    221 rdf:type schema:CreativeWork
    222 sg:pub.10.1038/ncomms6352 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018009622
    223 https://doi.org/10.1038/ncomms6352
    224 rdf:type schema:CreativeWork
    225 sg:pub.10.1038/ncomms9425 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037681456
    226 https://doi.org/10.1038/ncomms9425
    227 rdf:type schema:CreativeWork
    228 sg:pub.10.1038/nmeth.3515 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001171659
    229 https://doi.org/10.1038/nmeth.3515
    230 rdf:type schema:CreativeWork
    231 sg:pub.10.1038/nsb0298-140 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052877349
    232 https://doi.org/10.1038/nsb0298-140
    233 rdf:type schema:CreativeWork
    234 https://doi.org/10.1002/anie.200904035 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047561132
    235 rdf:type schema:CreativeWork
    236 https://doi.org/10.1016/j.bbapap.2014.03.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024562392
    237 rdf:type schema:CreativeWork
    238 https://doi.org/10.1016/j.chembiol.2008.10.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038423096
    239 rdf:type schema:CreativeWork
    240 https://doi.org/10.1016/j.febslet.2007.06.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005289941
    241 rdf:type schema:CreativeWork
    242 https://doi.org/10.1016/j.febslet.2012.01.029 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021358073
    243 rdf:type schema:CreativeWork
    244 https://doi.org/10.1016/j.jmb.2008.02.045 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034884603
    245 rdf:type schema:CreativeWork
    246 https://doi.org/10.1016/j.jmb.2009.10.030 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010352193
    247 rdf:type schema:CreativeWork
    248 https://doi.org/10.1016/j.molcel.2009.07.027 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038287493
    249 rdf:type schema:CreativeWork
    250 https://doi.org/10.1016/s0014-5793(00)01198-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024430074
    251 rdf:type schema:CreativeWork
    252 https://doi.org/10.1016/s0022-2836(02)00260-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023347934
    253 rdf:type schema:CreativeWork
    254 https://doi.org/10.1016/s0022-2836(05)80265-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001603185
    255 rdf:type schema:CreativeWork
    256 https://doi.org/10.1016/s0092-8674(00)80342-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026580014
    257 rdf:type schema:CreativeWork
    258 https://doi.org/10.1016/s0969-2126(99)80092-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046343057
    259 rdf:type schema:CreativeWork
    260 https://doi.org/10.1021/acschembio.6b00765 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055135344
    261 rdf:type schema:CreativeWork
    262 https://doi.org/10.1021/acssynbio.5b00197 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055140769
    263 rdf:type schema:CreativeWork
    264 https://doi.org/10.1021/bi3016185 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039406946
    265 rdf:type schema:CreativeWork
    266 https://doi.org/10.1021/ja058262u schema:sameAs https://app.dimensions.ai/details/publication/pub.1005213075
    267 rdf:type schema:CreativeWork
    268 https://doi.org/10.1021/ja5069728 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013286517
    269 rdf:type schema:CreativeWork
    270 https://doi.org/10.1021/ol300045c schema:sameAs https://app.dimensions.ai/details/publication/pub.1056252641
    271 rdf:type schema:CreativeWork
    272 https://doi.org/10.1073/pnas.0601756103 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044268128
    273 rdf:type schema:CreativeWork
    274 https://doi.org/10.1073/pnas.0704769104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019469535
    275 rdf:type schema:CreativeWork
    276 https://doi.org/10.1073/pnas.0804157105 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000818675
    277 rdf:type schema:CreativeWork
    278 https://doi.org/10.1073/pnas.1419737111 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007847065
    279 rdf:type schema:CreativeWork
    280 https://doi.org/10.1073/pnas.79.17.5200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049618417
    281 rdf:type schema:CreativeWork
    282 https://doi.org/10.1074/jbc.m112.396754 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035619483
    283 rdf:type schema:CreativeWork
    284 https://doi.org/10.1093/nar/gkv800 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017566530
    285 rdf:type schema:CreativeWork
    286 https://doi.org/10.1126/science.1077464 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009906122
    287 rdf:type schema:CreativeWork
    288 https://doi.org/10.1126/science.1241459 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011644178
    289 rdf:type schema:CreativeWork
    290 https://doi.org/10.1128/jb.175.6.1856-1859.1993 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062722498
    291 rdf:type schema:CreativeWork
    292 https://doi.org/10.1146/annurev-biochem-060713-035737 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042649778
    293 rdf:type schema:CreativeWork
    294 https://doi.org/10.1146/annurev.biochem.052308.105824 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032969013
    295 rdf:type schema:CreativeWork
    296 https://doi.org/10.1371/journal.pone.0002387 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013268232
    297 rdf:type schema:CreativeWork
    298 https://www.grid.ac/institutes/grid.38142.3c schema:alternateName Harvard University
    299 schema:name Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
    300 rdf:type schema:Organization
    301 https://www.grid.ac/institutes/grid.411017.2 schema:alternateName University of Arkansas at Fayetteville
    302 schema:name Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA.
    303 rdf:type schema:Organization
    304 https://www.grid.ac/institutes/grid.47100.32 schema:alternateName Yale University
    305 schema:name Department of Chemistry, Yale University, New Haven, Connecticut, USA.
    306 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
    307 rdf:type schema:Organization
    308 https://www.grid.ac/institutes/grid.66859.34 schema:alternateName Broad Institute
    309 schema:name Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
    310 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
    311 Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA.
    312 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...