Two‐Enzyme Hydrogen‐Borrowing Amination of Alcohols Enabled by a Cofactor‐Switched Alcohol Dehydrogenase

Abstract

The NADPH‐dependent secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus (TeSADH), displaying broad substrate specificity and low enantioselectivity, was engineered to accept NADH as a cofactor. The engineered TeSADH showed a >10 000‐fold switch from NADPH towards NADH compared to the wildtype enzyme. This TeSADH variant was applied to a biocatalytic hydrogen‐borrowing system that employed catalytic amounts of NAD+, ammonia, and an amine dehydrogenase, which thereby enabled the conversion a range of alcohols into chiral amines.

Enhancing cofactor recycling in the bioconversion of racemic alcohols to chiral amines with alcohol dehydrogenase and amine dehydrogenase by coupling cells and cell‐free system

“…Seventy‐one percent conversion was obtained at 12 hr, giving 14.1 mM ( R )‐ 3a in 99% ee , with a TTN for NADH recycling of 1410. To the best of our knowledge, this was the highest TTN ever reported in ADH–AmDH‐catalyzed cascade transformation of alcohols to amines (TTN, <40; Knaus et al, ; Mutti et al, ; Thompson & Turner, ). The incomplete conversion of ketone 2a to amine 3a was mainly due to the low catalytic efficiency of the AmDH ( k cat / K m : 10 2 –10 3 ; Abrahamson et al, ; Ye et al, ).…”

Sequential Two‐Step Stereoselective Amination of Allylic Alcohols through the Combination of Laccases and Amine Transaminases

“…Biocatalytic methods have emerged as a sustainable solution for the synthesis of chiral amines by means of the single action of enzymes of several classes, including lipases, amine transaminases (ATAs), amine oxidases, amine dehydrogenases, imine reductases or reductive aminases, but, interestingly, great efforts have in recent years been devoted to the synthesis of chiral amines through chemo‐, photo‐ and multienzymatic approaches . As an example, the selective amination of racemic sec ‐alcohols through elegant cascades based on the combination of alcohol‐dehydrogenase‐catalysed oxidation to ketones with subsequent bioamination by using ATAs or amine dehydrogenases has been described. In spite of these efforts, the biocatalytic synthesis of (3 E )‐4‐arylbut‐3‐en‐2‐amines has received little attention, the activity of commercially available amine transaminases for the bio‐transamination of (3 E )‐4‐phenylbut‐3‐en‐2‐one into optically active (3 E )‐4‐phenylbut‐3‐en‐2‐amine being low (<30 %) …”

A biocatalytic cascade for the amination of unfunctionalised cycloalkanes

“…31,32 Moreover, biocatalytic redox-neutral hydrogen-borrowing processes have been demonstrated for the conversion of alcohols into the corresponding primary amines. [33][34][35] Thus far, these studies are limited to the synthesis of primary amines due to the nature and specificity of the amination biocatalyst. However, recently we have demonstrated the synthesis of aliphatic and aromatic secondary amines starting from primary and secondary alcohols via hydrogen-borrowing employing a single alcohol dehydrogenase (ADH) and the newly characterised AspRedAm.…”