Exploring the Substrate Scope and Catalytic Promiscuity of Nitroreductase‐like Enzymes

Flavin-dependent nitroreductases are gaining attention as biocatalysts for the synthesis of pharmaceutically active compounds and their precursors. Here, we examined a panel of nitroreductase-like flavoenzymes for their reductase activity towards a wide variety of aromatic and aliphatic nitro compounds, nitroolefins, and α,β-unsaturated carbonyl compounds. Several of these flavoenzymes displayed high reductase activity and achieved excellent conversion of diverse nitroarenes, nitroolefins and α,β-unsaturated carbonyl compounds, accomplishing good product yields in semi-preparative scale reactions (up to 97%). In addition to the catalytic promiscuity of several of these flavoenzymes, being able to perform the reduction of nitro groups (nitroreductase activity) as well as C=C groups (ene-reductase activity), this study also revealed that some flavoenzymes exhibit high chemo-, regio- and/or enantioselectivity, making them attractive enzymes for use in organic synthesis.