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.
Highlights
Pure amines are indispensable constituents of various small molecule pharmaceuticals, fine chemicals, and agrochemicals [1]
Biocatalysis kinetic resolution of the racemic mixture of amines; (B) asymmetric synthesis using pro-chiral ketones ω-TAs can be employed for the synthesis of enantiopure amines using three approaches: (A)
(1) Use of lactose dehydrogenase (LDH) and NADH recycling system [53], wherein pyruvate is reduced to lactate, which is recycled using glucose dehydrogenase at the expense of cheaper substrate i.e., glucose (Figure 3B). (2) Use of alanine dehydrogenase (AlaDH) for the effective recycling of L-alanine as amine donor has been reported to reduce the cost of amine donor by 97%, while simultaneously decreasing the E-factor and improving the atom efficiency [54]
Summary
Pure amines are indispensable constituents of various small molecule pharmaceuticals, fine chemicals, and agrochemicals [1]. L -alanine to form pyridoxamine phosphate (PMP) intermediate This amine amineasgroup is transferred to the amino acceptor, such as a keto acid or ketone and the PLP is group is transferred thecatalytic amino acceptor, such as a The keto enantiomeric acid or ketonepurity and the regenerated regenerated for the to cycle [12,18,21]. Biocatalysis kinetic resolution of the racemic mixture of amines; (B) asymmetric synthesis using pro-chiral ketones ω-TAs can be employed for the synthesis of enantiopure amines using three approaches: (A). The previous two decades have seen a surge of kinetic resolution of the racemic mixture of amines; (B) asymmetric synthesis using pro-chiral interest in TA-mediated amination reactions. Deracemization racemic (S)-ω-TA. (Adapted from [14], Copyright (2010), with permission from Elsevier)
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