Cupin Variants as a Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes
Angew. Chem. 2020, 132, 7791-7794, 10.1002/ange.202000129
Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded β-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantioselective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, calculated substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.
Metal: CuLigand type: Amino acidHost protein: Cupin superfamily protein (TM1459)Anchoring strategy: DativeOptimization: Chemical & geneticReaction: Michael additionMax TON: 250ee: 99PDB: 6L2DNotes: ---