Imine reductases are nicotinamide-dependent enzymes that catalyze the asymmetric reduction of various imines to the corresponding amine products. Owing to the increasing roles of chiral amines and heterocyclic compounds as intermediates for pharmaceuticals, the demand for novel selective synthesis strategies is vitally important. Recent studies have demonstrated the discovery and structural characterization of a number of stereoselective imine reductase enzymes. Here, we highlight recent progress in applying imine reductases for the formation of chiral amines and heterocycles. It particularly focuses on the utilization of imine reductases in reductive aminations of aldehydes and ketones with various amine nucleophiles, one of the most powerful reactions in the synthesis of chiral amines. Second, we report on the synthesis of saturated substituted N-heterocycles by combining them with further biocatalysts, such as carboxylic acid reductases, oxidases or transaminases. Finally, we summarize the latest applications of imine reductases in the promiscuous asymmetric hydrogenation of a highly reactive carbonyl compound and the engineering of the cofactor specificity from NADPH to NADH.

We designed a novel H2-driven cascade for the biosynthesis of N-heterocycles.

Synthesis of 3‐methylpiperidine from 1,5‐diamino‐2‐methylpentane in preparative scale is reported by using recombinant Escherichia coli cells expressing a variant of the diamine oxidase from Rhodococcus erythroprolis and an imine reductase from Streptosporangium roseum. Optimization of process parameters for cultivation and bioconversion led to substantial improvements in the initial laboratory procedure. The transformation of the methyl‐substituted diamine substrate to the N‐heterocyclic product was successfully scaled‐up from shake‐flask to a 20 L bioreactor with increased substrate concentrations. Remarkably, we obtained 67 % of 3‐methylpiperidine product from 140 g substrate within 52 h.