Recent Advances in ω-Transaminase-Mediated Biocatalysis for the Enantioselective Synthesis of Chiral Amines

Abstract

Chiral amines are important components of 40-45% of small molecule pharmaceuticals and many other industrially important fine chemicals and agrochemicals. Recent advances in synthetic applications of ω-transaminases for the production of chiral amines are reviewed herein. Although a new pool of potential ω-transaminases is being continuously screened and characterized from various microbial strains, their industrial application is limited by factors such as disfavored reaction equilibrium, poor substrate scope, and product inhibition. We present a closer look at recent developments in overcoming these challenges by various reaction engineering approaches. Furthermore, protein engineering techniques, which play a crucial role in improving the substrate scope of these biocatalysts and their operational stability, are also presented. Last, the incorporation of ω-transaminases in multi-enzymatic cascades, which significantly improves their synthetic applicability in the synthesis of complex chemical compounds, is detailed. This analysis of recent advances shows that ω-transaminases will continue to provide an efficient alternative to conventional catalysis for the synthesis of enantiomerically pure amines.

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

“…At this point the bio‐transamination experiments with (3 E )‐4‐(het)arylbut‐3‐en‐2‐ones 2 a – p were assayed, in order to identify not only acceptable reaction conditions but also suitable amine transaminases (ATAs) for each substrate, so that the stereoselective amination of the racemic alcohols might be attempted later in a concurrent approach. Pyridoxal‐5′‐phosphate (PLP)‐dependent ATAs have been found to be ideal biocatalysts for the transformation of prochiral and racemic ketones into optically active amines by using a molar excess of an amine donor, generally isopropylamine or alanine . For simplicity, an initial assessment was developed with ketone 2 a and the commercially available R ‐selective ATA‐024, which is known to accept isopropylamine as amine donor.…”

Transaminases for industrial biocatalysis: novel enzyme discovery

“…There have been a number of excellent TAm reviews written in recent years, focusing on a range of topics including classification, application, engineering, and optimization of TAms and their reactions (Guo and Berglund 2017;Ferrandi and Monti 2018;Gomm and O'Reilly 2018;Kelly et al 2018a;Patil et al 2018). This mini-review will focus on the approaches used in novel wild-type TAm discovery over the past two decades, highlighting the changing trends in the field during this time.…”

The Catalytic Mechanism of Human Transketolase

“…[4,5] Additionally, tumor cells growth has been blocked by inhibiting non-oxidative phase of PPP in which hTK is involved [6,7] and, moreover, the reduced activities of hTK have been linked to diseases affecting brain tissues, such as Alzheimer's disease. [1,13,[17][18][19][20] Since the product of this last process is a highly reactive species, ThDP-dependent enzymes are widely adopted in relevant processes for several chemoenzymatic synthesis involving the formation or the cleavage of CÀ S, CÀ N, CÀ C and CÀ O bonds, [21][22][23][24][25][26][27][28] as well as the sustainable and ecofriendly asymmetric carboligation of both aliphatic and aromatic compounds. In physiological conditions, it was observed that hTK requires the presence of the thiamine diphosphate (ThDP) cofactor as co-catalytic agent.…”