Successful exploitation of biocatalytic processes employing flavoproteins requires the implementation of cost-effective solutions to circumvent the need to supply costly nicotinamide coenzymes as reducing equivalents. Chemical syntheses harnessing the power of the flavoprotein ene reductases will likely increase the range and/or optical purity of available fine chemicals and pharmaceuticals due to their ability to catalyze asymmetric bioreductions. This review will outline current progress in the design of alternative routes to ene reductase flavin activation, most notably within the Old Yellow Enzyme family. A variety of chemical, enzymatic, electrochemical and photocatalytic routes have been employed, designed to eliminate the need for nicotinamide coenzymes or provide cost-effective alternatives to efficient recycling. Photochemical approaches have also enabled novel mechanistic routes of ene reductases to become available, opening up the possibility of accessing a wider range of non-natural chemical diversity.
Keywords: Chemoenzymatic; Cofactor recycling; Electroenzymatic; Ene reductase; Flavoprotein; NAD(P)H; Nicotinamide mimetics; Old Yellow Enzyme; Photoenzyme.
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