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dc.contributor.authorMangas-Sanchez, Juan; orcid: 0000-0002-3364-1512
dc.contributor.authorSharma, Mahima; orcid: 0000-0003-3960-2212
dc.contributor.authorCosgrove, Sebastian C; orcid: 0000-0001-9541-7201
dc.contributor.authorRamsden, Jeremy I
dc.contributor.authorMarshall, James R
dc.contributor.authorThorpe, Thomas W
dc.contributor.authorPalmer, Ryan B
dc.contributor.authorGrogan, Gideon
dc.contributor.authorTurner, Nicholas J; orcid: 0000-0002-8708-0781
dc.date.accessioned2021-07-16T02:17:27Z
dc.date.available2021-07-16T02:17:27Z
dc.date.issued2020-05-05
dc.identifierpmcid: PMC8159254
dc.identifierdoi: 10.1039/d0sc02253e
dc.identifierpmid: 34122962
dc.identifier.citationChemical science, volume 11, issue 19, page 5052-5057
dc.identifier.urihttp://hdl.handle.net/10034/625272
dc.descriptionFrom Europe PMC via Jisc Publications Router
dc.descriptionHistory: ppub 2020-05-01, epub 2020-05-05
dc.descriptionPublication status: Published
dc.descriptionFunder: Biotechnology and Biological Sciences Research Council; Grant(s): BB/M006832/1
dc.descriptionFunder: European Research Council; Grant(s): 742987
dc.descriptionFunder: Engineering and Physical Sciences Research Council; Grant(s): EP/S01778X/1
dc.description.abstractChiral primary amines are important intermediates in the synthesis of pharmaceutical compounds. Fungal reductive aminases (RedAms) are NADPH-dependent dehydrogenases that catalyse reductive amination of a range of ketones with short-chain primary amines supplied in an equimolar ratio to give corresponding secondary amines. Herein we describe structural and biochemical characterisation as well as synthetic applications of two RedAms from <i>Neosartorya</i> spp. (<i>Nf</i>RedAm and <i>Nfis</i>RedAm) that display a distinctive activity amongst fungal RedAms, namely a superior ability to use ammonia as the amine partner. Using these enzymes, we demonstrate the synthesis of a broad range of primary amines, with conversions up to >97% and excellent enantiomeric excess. Temperature dependent studies showed that these homologues also possess greater thermal stability compared to other enzymes within this family. Their synthetic applicability is further demonstrated by the production of several primary and secondary amines with turnover numbers (TN) up to 14 000 as well as continous flow reactions, obtaining chiral amines such as (<i>R</i>)-2-aminohexane in space time yields up to 8.1 g L<sup>-1</sup> h<sup>-1</sup>. The remarkable features of <i>Nf</i>RedAm <i>and Nfis</i>RedAm highlight their potential for wider synthetic application as well as expanding the biocatalytic toolbox available for chiral amine synthesis.
dc.languageeng
dc.rightsLicence for this article: cc by-nc
dc.sourceissn: 2041-6520
dc.sourceessn: 2041-6539
dc.sourcenlmid: 101545951
dc.titleAsymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases.
dc.typearticle
dc.date.updated2021-07-16T02:15:55Z


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