title: Chiral amine synthesis using ω-transaminases: an amine donor that displaces equilibria and enables high-throughput screening.
abstract: The widespread application of ω-transaminases as biocatalysts for chiral amine synthesis has been hampered by fundamental challenges, including unfavorable equilibrium positions and product inhibition. Herein, an efficient process that allows reactions to proceed in high conversion in the absence of by-product removal using only one equivalent of a diamine donor (ortho-xylylenediamine) is reported. This operationally simple method is compatible with the most widely used (R)- and (S)-selective ω-TAs and is particularly suitable for the conversion of substrates with unfavorable equilibrium positions (e.g., 1-indanone). Significantly, spontaneous polymerization of the isoindole by-product generates colored derivatives, providing a high-throughput screening platform to identify desired ω-TA activity.
authors.affiliation: School of Chemistry, Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN (UK). anthony.green@manchester.ac.uk.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Green
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Turner
authors.forename: Elaine
authors.initials: E
authors.lastname: O'Reilly
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D057166:High-Throughput Screening Assays; D009346:Neisseriaceae / Q000201:enzymology*; D058105:Polymerization; D013237:Stereoisomerism; D000637:Transaminases / Q000378:metabolism*; D014992:Xylenes / Q000737:chemistry / Q000378:metabolism
chemical_list: D000588:Amines; D014992:Xylenes; C066883:1,3-xylenediamine; D000637:Transaminases
keywords: asymmetric catalysis; biocatalysis; chiral amines; high-throughput screening; transaminases