Artificial metalloenzymes (ArMs) provide a unique platform to integrate the reactivity of homogenous organometallic catalysis and the selectivity and evolvability of enzymes. ArMs can be used to design new-to-nature biocatalysts and enzymatic cascades. Herein, we describe the engineering and evolution of dirhodium ArMs for selective carbene transfer catalysis. Specifically, we evolved the enantiocontrol of dirhodium ArMs from 40% to 73% for N-H insertion and from 71% to 93% for Si-H insertion reactions. The activity of dirhodium ArMs was also increased almost 2-fold for Si-H insertion in this process. The improved activity of dirhodium ArMs for Si-H insertion translates into C-H insertion using a mechanism-guided directed evolution approach. The innate structural information and conformational dynamics of the protein scaffold Pyrococcus furiosus prolyl oligopeptidase (Pfu POP) will help us understand not only the nature of evolvability of Pfu POP but also its ability to control mechanistically diverse reactions. This overall process of improving scaffold-based control over chemo and stereoselectivity towards multiple carbene transfer reactions will further our understanding of scaffold-based control over non-native metalloenzyme catalysis.

Dirhodium artificial metalloenzymes for selective carbene transfer reactions

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