title: Whole-Cell Biocatalysts for Stereoselective C-H Amination Reactions.
abstract: Enantiomerically pure chiral amines are ubiquitous chemical building blocks in bioactive pharmaceutical products and their synthesis from simple starting materials is of great interest. One of the most attractive strategies is the stereoselective installation of a chiral amine through C-H amination, which is a challenging chemical transformation. Herein we report the application of a multienzyme cascade, generated in a single bacterial whole-cell system, which is able to catalyze stereoselective benzylic aminations with ee values of 97.5%. The cascade uses four heterologously expressed recombinant enzymes with cofactors provided by the host cell and isopropyl amine added as the amine donor. The cascade presents the first example of the successful de novo design of a single whole-cell biocatalyst for formal stereoselective C-H amination.
authors.affiliation: School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0002-4969-9014
authors.initials: P
authors.lastname: Both
authors.affiliation: School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Hanna
authors.initials: H
authors.lastname: Busch
authors.affiliation: School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Kelly
authors.affiliation: School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Francesco G
authors.initials: FG
authors.lastname: Mutti
authors.affiliation: School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Turner
authors.affiliation: School of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK. Sabine.Flitsch@manchester.ac.uk.
authors.forename: Sabine L
authors.identifier: http://orcid.org/0000-0003-3974-646X
authors.initials: SL
authors.lastname: Flitsch
mesh_terms: D000586:Amination; D055162:Biocatalysis; D001711:Biotransformation; D002244:Carbon / Q000737:chemistry*; D002849:Chromatography, Gas; D004926:Escherichia coli / Q000378:metabolism; D006859:Hydrogen / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D002244:Carbon; D006859:Hydrogen
keywords: aminations; biocatalysis; chiral amines; enzyme cascades; whole-cell biotransformation