cover illustration Homologous imine reductases (IRED) and b-hydroxyacid dehydrogenases(bHADs) with similarly oriented active site residues were engineered for generating novel imine-reducing enzymes. Active site amino acid residues of bHADs were substituted with the corresponding residues from a R-selective IRED and then screened for promiscuous imine reduction activity. Analysis of the selected variants demonstrated how active site mutations alter the chemistry of IREDs and bHADs.