Chemo‐ and Enantioselective Photoenzymatic Ketone Reductions Using a Promiscuous Flavin‐dependent Nitroreductase

Flavoenzymes are oxidoreductases that catalyze an extensive range of different types of reactions. An advanced and powerful approach to achieving transformations that are normally outside the realm of flavoenzymes is the synergistic combination of photocatalysis and biocatalysis. Here we report the identification of a promiscuous flavin‐dependent nitroreductase, BaNTR1, that is able to promote enantioselective photobiocatalytic reductions of a broad range of structurally diverse ketones to yield the corresponding alcohols with high conversion (up to >99 %) and outstanding enantiopurity (up to >99 : 1 e.r). Noteworthy, BaNTR1 was able to promote the photoenzymatic reduction of various α,ß‐unsaturated ketones to give the corresponding optically pure alcohols without reducing the C=C or C≡C bond, illustrating its remarkably high chemoselectivity. Our results highlight the usefulness of photocatalysis for expanding the catalytic repertoire of nitroreductases to include highly enantio‐ and chemoselective reductions of non‐native ketone substrates to produce optically pure alcohols. This includes difficult to prepare allyl alcohols that are not accessible via photoenzymatic conversions using ene‐reductases. The enantioselective photoenzymatic reduction of a wide variety of ketones to the corresponding alcohols using the promiscuous nitroreductase BaNTR1 is reported. This flavoenzyme not only shows outstanding enantioselectivity but also remarkably high chemoselectivity, promoting the photoenzymatic reduction of various α,ß‐unsaturated ketones to give the desired enantioenriched alcohols without reducing the C=C or C≡C bond.