A New Generation of Smart Amine Donors for Transaminase‐Mediated Biotransformations

Abstract

The application of ω-transaminase biocatalysts for the synthesis of optically pure chiral amines presents a number of challenges, including difficulties associated with displacing the challenging reaction equilibria. Herein, we report a highly effective approach using low equivalents of the new diamine donor, cadaverine, which enables high conversions of challenging substrates to the corresponding chiral amines in excellent ee. This approach paves the way for the design of self-sufficient fermentation processes combining transaminase biotransformations with existing strategies for cadaverine production by decarboxylation of endogenous lysine.

Asymmetric Synthesis of Chiral Halogenated Amines using Amine Transaminases

“…For this purpose, pyruvate decarboxylase, alanine dehydrogenase, or, most commonly, a combination of lactate dehydrogenase and glucose dehydrogenase (LDH/GDH system) are applied to drive the desired transamination reaction to completeness. More recently, aliphatic diamines were reported as effective amine donors …”

“…reported the synthesis of ( S )‐1‐(5‐fluoropyrimidin‐2‐yl)ethylamine. Gomm et al., Green et al., and Martínez‐Monteroet al . subjected 4‐fluorophenylacetone to the asymmetric synthesis of the corresponding amine.…”

Isolation and Characterisation of a Halotolerant ω‐Transaminase from a Triassic Period Salt Mine and Its Application to Biocatalysis

“…Despite high profile successes of TAm use in the pharmaceutical industry, namely the production of the antidiabetic drug sitagliptin, there is a growing need for new enzymes with improved capabilities. The application of TAms is often hampered by a restricted substrate scope, lack of tolerance to harsh reaction conditions and an inability of enzymes to accept bulky substrates without considerable protein engineering …”

Development of an in situ‐Product Crystallization (ISPC)‐Concept to Shift the Reaction Equilibria of Selected Amine Transaminase‐Catalyzed Reactions

“…The transamination-reaction can be carried out as a kinetic resolution of a racemic amine or an asymmetric synthesis from the respective prochiral ketone. [22][23][24][25][26][27][28][29][30] Such techniques its reaction solution as a barely soluble salt effectively yields a displacement of the reaction equilibrium towards the products and facilitates a simple downstream processing approach via filtration. [16] Unfortunately, thermodynamic limitations and certain product inhibitions tend to limit the applicability of transaminases in asymmetric synthesis, which needs to be overcome for synthetic purposes.…”