In this study, we aimed to develop protein-based metal ligands to catalyze cis-selective cyclopropanation using the TM1459 cupin protein superfamily. Copper complexes with TM1459 mutants containing the 3-His metal-binding site exhibited excellent diastereoselectivity in cyclopropanation reactions with styrene and ethyl diazoacetate. Further mutations in the secondary coordination sphere increased the cis-preference with t-butyl diazoacetate as the substrate with up to 80 : 20 (cis:trans ratio) and high enantioselectivity (90 % ee).
Keywords: Artificial metalloenzymes; Cupin; Cyclopropanation; Metallocarbene; Mononuclear copper enzyme.
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