Imine reductases (IREDs) have emerged as valuable biocatalysts for the asymmetric synthesis of chiral amines, key intermediates in numerous active pharmaceutical ingredients. Their ability to operate under mild reaction conditions with high chemo- and stereoselectivity provides an attractive alternative to conventional metal-catalyzed or chemical reduction processes. However, the broader industrial application of wild-type IREDs is often constrained by their limited substrate scope and moderate catalytic efficiency. Recent advances in biocatalysis have demonstrated that engineered IREDs can catalyze the reduction of a wide range of natural and non-natural imines, significantly expanding their applicability in pharmaceutical and fine chemical synthesis. In parallel, enzyme immobilization strategies have proven highly effective for improving operational stability, facilitating enzyme reuse, and enabling continuous flow biocatalytic processes. Efficient cofactor regeneration systems have further enhanced the practical implementation of IRED-based transformations. Advances in protein engineering, including structure-guided design, semi-rational mutagenesis, and directed evolution, have generated enzyme variants with improved catalytic activity, stereoselectivity, and substrate tolerance. The integration of high-throughput screening technologies and machine-learning-assisted enzyme design has further accelerated the discovery and optimization of efficient IRED biocatalysts. This review summarizes recent progress in the protein engineering and immobilization of IREDs and discusses future perspectives for their industrial application.
Kaličanin et al. (Sat,) studied this question.