Amine transaminases are important biocatalysts for the synthesis of chiral primary amines. Unlike many enzymes that have been employed for the synthesis of optically active amines, amine transaminases are capable of asymmetric synthesis and do not rely on costly cofactors that must be regenerated in situ. However, their application as general catalysts for the preparation of amines is hampered by a limited substrate scope, substrate and (co)product inhibition and difficulties associated with displacing challenging reaction equilibrium. There has been important progress made to overcome these challenges, including the development of enzymes with broader substrate scope and the design of methodology to effectively displace the reaction equilibrium. Amine transaminases are also being applied in an increasing range of (chemo)enzymatic cascades and immobilized for applications in flow.

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.

ABSTRACT:The expanding "toolbox" of biocatalysts opens new opportunities to redesign synthetic strategies to target molecules by incorporating a key enzymatic step into the synthesis. Herein, we describe a general biocatalytic approach for the enantioselective preparation of 2,6-disubstituted piperidines starting from easily accessible prochiral ketoenones. The strategy represents a new biocatalytic disconnection, which relies on an ω-TA-mediated azaMichael reaction. Significantly, we show that the reversible enzymatic process can power the shuttling of amine functionality across a molecular framework, providing access to the desired aza-Michael products.

The “smart” amine donors o‐xylylenediamine and cadaverine were employed for the rapid screening of a large ketone library and subsequent preparative‐scale synthesis of selected compounds using a commercially available amine transaminase, ATA256. The methodology enables both screening and preparative‐scale biotransformations to be performed with a single enzyme and simplifies the generation of sp3‐rich small‐molecule libraries.

The conversion of readily available monosaccharides to high-value amino alcohols using a key biocatalytic step is an attractive strategy for the preparation of these chiral synthons. Here, we report a previously undescribed example of the direct amination of monosaccharides, which exist predominantly in their cyclic form at equilibrium, using amine transaminase biocatalysts, providing access to a panel of amino alcohols in moderate to high conversion and isolated yield. A recently developed high-throughput colorimetric screen, employing o-xylylenediamine, was initially used to identify amine transaminase enzymes displaying this activity towards cyclic sugars and reactions were successfully scaled-up using isopropylamine.