Artificial Metalloenzymes for Enantioselective Catalysis Based on the Noncovalent Incorporation of Organometallic Moieties in a Host Protein

Enzymatic and homogeneous catalysis offer complementary means to produce enantiopure products. Incorporation of achiral, biotinylated aminodiphosphine–rhodium complexes in (strept)avidin affords enantioselective hydrogenation catalysts. A combined chemogenetic procedure allows the optimization of the activity and the selectivity of such artificial metalloenzymes: the reduction of acetamidoacrylate proceeds to produce N-acetamidoalanine in either 96 % ee (R) or 80 % ee (S). In addition to providing a chiral second coordination sphere and, thus, selectivity to the catalyst, the phenomenon of protein-accelerated catalysis (e.g., increased activity) was unraveled. Such artificial metalloenzymes based on the biotin–avidin technology display features that are reminiscent of both homogeneous and of enzymatic catalysis.