Identification and Structure Analysis of an Unusual Halohydrin Dehalogenase for Highly Chemo‐, Regio‐ and Enantioselective Bio‐Nitration of Epoxides

We report the discovery of an unusual halohydrin dehalogenase, HHDHamb, that can work under relatively low acidic conditions and extremely low temperatures for the bio‐nitration of epoxides using nitrite as a nitrating agent. The bio‐nitration strategy exhibits high chemo‐, regio‐, and enantioselectivity, catalyzing the kinetic resolution of various epoxides to enantiopure β‐nitroalcohols with nitro‐bearing stereocenters in up to 41 % isolated yield and >99 % enantiomeric excess (ee). Additionally, the bio‐nitration method displays a high reaction efficiency and can be performed on a gram scale. We also solved the crystal structure of HHDHamb to understand the possible structural determinants of chemoselectivity control in the bio‐nitration reaction. An unusual halohydrin dehalogenase HHDHamb was identified for highly chemo‐, regio‐ and enantioselective bio‐nitration of epoxides. Enantiopure β‐nitroalcohols containing nitro‐bearing stereocenters were synthesized on preparative scale by whole‐cell biotransformation. The enzyme structure was also solved and analyzed, providing a possible understanding of the chemoselectivity control mechanism in the bio‐nitration reaction.