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Design and Evolution of an Artificial Aldolase with an Abiological Catalytic Cofactor in Apo-Myoglobin
Qinru Hu1, Liangyu Feng1, Ran You1
1School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China.
Abstract:
Current research on artificial aldolases predominantly centers on aldehyde substrates with relatively limited exploration of ketone substrates. Here, we report the creation of a novel artificial aldolase based on apo-myoglobin by embedding an organocatalytic secondary amine cofactor in the protein's distal pocket. The designer enzyme exhibits good to excellent enantioselectivities (up to 97.5:2.5 er) for couplings of acetone with diverse aldehyde substrates. This work establishes apo-myoglobin as a versatile chassis for integrating abiological organocatalysts and demonstrates that combining non-natural cofactors with directed evolution can unlock C-C bond-forming reactivities.
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