A reductive aminase from Aspergillus oryzae

Abstract

Reductive 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 d.

Chemoenzymatic Approaches to the Synthesis of the Calcimimetic Agent Cinacalcet Employing Transaminases and Ketoreductases

“…Besides, a drawback could arise from the unfavorable equilibrium of imine formation in water for 3 even though some substantial evidences have recently supported the imine formation in the active site of some IREDs with a selection of ketone and amine partners (Scheme 2). 10d Further attempts performed with the chemically synthesized imine 6 and IREDs did not show conversion in any case.…”

Terminal Alkenes from Acrylic Acid Derivatives via Non‐Oxidative Enzymatic Decarboxylation by Ferulic Acid Decarboxylases

“…In view of the fact that biocatalytic transformations are operational under mild and environmentally‐friendly conditions and proceed with high chemo‐, regio‐ and stereoselectivity,7 there is an increasing interest in expanding the scope and efficiency of enzymatic reactions 8, 9, 10, 11, 12, 13. Biological routes towards alkenes are rare and have been investigated only recently 14, 15, 16, 17, 18, 19, 20.…”

Direct Alkylation of Amines with Primary and Secondary Alcohols through Biocatalytic Hydrogen Borrowing

“…[13][14][15] Biocatalysis offers avariety of methods for the asymmetric synthesis of amines,i ncluding transaminases (TAs), monoamine oxidases (MAO-N), phenylalanine ammonia lyases (PALs), amine dehydrogenases (AmDHs), and imine reductases (IREDs). [25][26][27] Recently,w er eported the discovery of anew enzyme,areductive aminase from Aspergillus oryzae (AspRedAm), [28] which catalyzes the reductive amination of av ariety of carbonyl compounds at low amine loadings with good to excellent stereoselectivity.T his discovery prompted us to consider the application of AspRedAm in the hydrogenborrowing amination of alcohols. [25][26][27] Recently,w er eported the discovery of anew enzyme,areductive aminase from Aspergillus oryzae (AspRedAm), [28] which catalyzes the reductive amination of av ariety of carbonyl compounds at low amine loadings with good to excellent stereoselectivity.T his discovery prompted us to consider the application of AspRedAm in the hydrogenborrowing amination of alcohols.…”