Genome mining and characterisation of a novel transaminase with remote stereoselectivity

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dc.contributor.authorGavin, Declan P.
dc.contributor.authorReen, F. Jerry
dc.contributor.authorRocha-Martin, J.
dc.contributor.authorAbreu-Castilla, I.
dc.contributor.authorWoods, David F.
dc.contributor.authorFoley, Aoife M.
dc.contributor.authorSanchez-Murcia, P. A.
dc.contributor.authorSchwarz, Maria
dc.contributor.authorO'Neill, P.
dc.contributor.authorMaguire, Anita R.
dc.contributor.authorO'Gara, Fergal
dc.contributor.funderEnterprise Irelanden
dc.contributor.funderHealth Research Boarden
dc.contributor.funderIrish Thoracic Societyen
dc.contributor.funderEuropean Commissionen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Council for Science, Engineering and Technologyen
dc.contributor.funderCystic Fibrosis Foundationen
dc.contributor.funderAustrian Science Funden
dc.date.accessioned2022-02-25T16:29:25Z
dc.date.available2022-02-25T16:29:25Z
dc.date.issued2019-12-30
dc.date.updated2022-02-25T15:04:54Z
dc.description.abstractMicrobial enzymes from pristine niches can potentially deliver disruptive opportunities in synthetic routes to Active Pharmaceutical Ingredients and intermediates in the Pharmaceutical Industry. Advances in green chemistry technologies and the importance of stereochemical control, further underscores the application of enzyme-based solutions in chemical synthesis. The rich tapestry of microbial diversity in the oceanic ecosystem encodes a capacity for novel biotransformations arising from the chemical complexity of this largely unexplored bioactive reservoir. Here we report a novel omega-transaminase discovered in a marine sponge Pseudovibrio sp. isolate. Remote stereoselection using a transaminase has been demonstrated for the first time using this novel protein. Application to the resolution of an intermediate in the synthesis of sertraline highlights the synthetic potential of this novel biocatalyst discovered through genomic mining. Integrated chemico-genomics revealed a unique substrate profile, while molecular modelling provided structural insights into this 'first in class' selectivity at a remote chiral centre.en
dc.description.sponsorshipEnterprise Ireland ((CF-2017-0757-P; IP-2015-0390); Health Research Board/Irish Thoracic Society (MRCG-2018-16; MRCG-2014-6); European Commission ((EU2020-634486-2015); Science Foundation Ireland (SFI09/RFP/BMT2350); Irish Research Council for Science, Engineering and Technology (GOIPG/2014/647); Cystic Fibrosis Foundation, USA (OG1710); Austrian FWF (Project M 2260)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid20285en
dc.identifier.citationGavin, Declan P.; Reen, F. Jerry; Rocha-Martin, J.; Abreu-Castilla, I.;Woods, David F.;Foley, Aoife M.;Sanchez-Murcia, P. A.;Schwarz, Maria;O'Neill, P.;Maguire, Anita R.; O'Gara, Fergal (2019) 'Genome mining and characterisation of a novel transaminase with remote stereoselectivity', Scientific Reports, 9, 20285 (15 pp). doi: 10.1038/s41598-019-56612-7en
dc.identifier.doi10.1038/s41598-019-56612-7en
dc.identifier.endpage15en
dc.identifier.issn2045-2322
dc.identifier.journaltitleScientific Reportsen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/12604
dc.identifier.volume9en
dc.language.isoenen
dc.publisherSpringer Nature Switzerland AGen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/15/TIDA/2977/IE/Pre-clinical testing of novel fungal biofilm blockers for the medical device sector./en
dc.rights© The Author(s) 2019. This is an open access article under the terms of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectAsymmetric-synthesisen
dc.subjectChiral aminesen
dc.subjectMediated resolutionen
dc.subjectDirected evolutionen
dc.subjectKinetic resolutionen
dc.subjectOne-poten
dc.subjectEfficienten
dc.subjectOxidaseen
dc.subjectCascadeen
dc.subjectProteinen
dc.titleGenome mining and characterisation of a novel transaminase with remote stereoselectivityen
dc.typeArticle (peer-reviewed)en
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