The Discovery of Imine Reductases and their Utilisation for the Synthesis of Tetrahydroisoquinolines.

Imine reductases (IREDs) are NADPH-dependent enzymes with significant biocatalytic potential for the synthesis of primary, secondary, and tertiary chiral amines. Their applications include the reduction of cyclic imines and the reductive amination of prochiral ketones. In this study, twenty-nine novel IREDs were revealed through genome mining. Imine reductase activities were screened at pH 7 and 9 and in presence of either NADPH or NADH; some IREDs showed good activities at both pHs and were able to accept both cofactors. IREDs with Asn and Glu at the key 187 residue showed preference for NADH. IREDs were also screened against a series of dihydroisoquinolines to synthesise tetrahydroisoquinolines (THIQs), bioactive alkaloids with a wide range of therapeutic properties. Selected IREDs showed high stereoselectivity, as well high THIQ yields (>90 %) when coupled to a glucose-6-phosphate dehydrogenase for NADPH cofactor recycling.