No abstract

A major challenge in chemical synthesis is to develop catalytic systems that convert simple molecules to complex high-value products. Often these valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of the molecule. Of great interest are enantioenriched amine diastereomers, which are prevalent in pharmaceuticals and agrochemicals, 1 yet their preparation often relies on low-e ciency multi-step synthesis. 2 Herein, we report the discovery and characterisation of a multi-functional biocatalyst, which operates using a previously unreported conjugate reduction-reductive amination mechanism. This enzyme (pIR-120), identi ed within a metagenomic imine reductase (IRED) collection 3 and originating from an unclassi ed Pseudomonas species, possesses an unusual active site architecture that facilitates an amine-activated conjugate alkene reduction followed by reductive amination. This enzyme enables the coupling of a broad selection of α,β-unsaturated carbonyls with amines for the e cient preparation of enantioenriched amine diastereomers. Moreover, employing a racemic substrate partner or conjugated dienyl-ketone provides a means of controlling additional stereocentres using the single catalyst. Mechanistic and structural studies have been carried out to delineate the order of individual steps catalysed by pIR-120 which have led to a proposal for the overall catalytic cycle. This work shows that the IRED family can serve as a platform for facilitating the discovery of further enzymatic activities for application in synthetic biology and organic synthesis.

Fungal reductive aminases as effective biocatalysts for the preparation of chiral primary amines.

Ene-reductases (EREDs) catalyse the reduction of electron-deficient C=C bonds. Herein, we report the first example of ERED-catalysed net reduction of C=C bonds of enimines (α,βunsaturated imines). Preliminary studies suggest their hydrolysed ring-open ω-amino enones are the likely substrates for this step. When combined with imine reductase (IRED)-mediated C=N reduction, the result is an efficient telescoped sequence for the preparation of diastereomerically enriched 2-substituted saturated amine heterocycles.