Redox Out of the Box: Catalytic Versatility Across NAD(P)H‐Dependent Oxidoreductases

Abstract

The asymmetric reduction of double bonds using NAD(P)H‐dependent oxidoreductases has proven to be an efficient tool for the synthesis of important chiral molecules in research and on industrial scale. These enzymes are commercially available in screening kits for the reduction of C=O (ketones), C=C (activated alkenes), or C=N bonds (imines). Recent reports, however, indicate that the ability to accommodate multiple reductase activities on distinct C=X bonds occurs in different enzyme classes, either natively or after mutagenesis. This challenges the common perception of highly selective oxidoreductases for one type of electrophilic substrate. Consideration of this underexplored potential in enzyme screenings and protein engineering campaigns may contribute to the identification of complementary biocatalytic processes for the synthesis of chiral compounds. This review will contribute to a global understanding of the promiscuous behavior of NAD(P)H‐dependent oxidoreductases on C=X bond reduction and inspire future discoveries with respect to unconventional biocatalytic routes in asymmetric synthesis.

Unlocking the function promiscuity of old yellow enzyme to catalyze asymmetric Morita-Baylis-Hillman reaction

“…OYEs belong to a class of ene-reductases, primarily used for catalyzing the reduction of C = C bonds. In earlier studies, the function promiscuity of ene-reductases was mainly associated with the reduction of C = X bonds, including promiscuously capabilities for reducing C = N 34 , 35 , N = O, and O = O bonds 36 . Currently, research on the function promiscuity of ene-reductases has mostly focused on the field of photocatalysis for C-C bond formation, such as radical cyclization reactions 11 and intermolecular radical alkene alkylation reactions 37 .…”

Biocatalysis for the Synthesis of Active Pharmaceutical Ingredients in Deep Eutectic Solvents: State-of-the-Art and Prospects

“…Amongst them, ADHs are mostly used in the asymmetric reduction of ketones for the synthesis of various value-added chiral alcohols [111]. ADHs are cofactor-dependent and require a stoichiometric amount of costly NAD(P)H. The in situ cofactor-regeneration is proposed to enable a cost-effective application [112][113][114][115]. That necessity can be fulfilled by either in vivo designer cell systems or in vitro artificial regeneration systems, using an ancillary substrate [116].…”