5g6r
Imine reductase from Aspergillus oryzae
Structural highlights
FunctionREDAM_ASPOR NADPH-dependent reductive aminase that catalyzes the reductive coupling of a broad set of carbonyl compounds with a variety of primary and secondary amines (Ref.2). Possesses remarkably high activity for the reductive amination of ketones and amines, often with high stereoselectivity and in some cases with ketone:amine ratios as low as 1:1 (Ref.2). The cofactor NADPH, the carbonyl compound and the amine are added to the enzyme in that sequence, followed by the release of product, NADP(+) being released at last (Ref.2). RedAm is also able to act in the reverse, oxidative direction and exhibits activity in the dehydrogenation of amines to yield imines (Ref.2). The highest activity is found for 1-methyl-tetrahydroquinoline and acyclic amines are also found to be transformed (Ref.2).[REFERENCE:2] Publication Abstract from PubMedReductive amination is one of the most important methods for the synthesis of chiral amines. Here we report the discovery of an NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm, Uniprot code Q2TW47) that can catalyse the reductive coupling of a broad set of carbonyl compounds with a variety of primary and secondary amines with up to >98% conversion and with up to >98% enantiomeric excess. In cases where both carbonyl and amine show high reactivity, it is possible to employ a 1:1 ratio of the substrates, forming amine products with up to 94% conversion. Steady-state kinetic studies establish that the enzyme is capable of catalysing imine formation as well as reduction. Crystal structures of AspRedAm in complex with NADP(H) and also with both NADP(H) and the pharmaceutical ingredient (R)-rasagiline are reported. We also demonstrate preparative scale reductive aminations with wild-type and Q240A variant biocatalysts displaying total turnover numbers of up to 32,000 and space time yields up to 3.73 g l-1 d-1. A reductive aminase from Aspergillus oryzae.,Aleku GA, France SP, Man H, Mangas-Sanchez J, Montgomery SL, Sharma M, Leipold F, Hussain S, Grogan G, Turner NJ Nat Chem. 2017 Oct;9(10):961-969. doi: 10.1038/nchem.2782. Epub 2017 May 29. PMID:28937665[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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