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bioRxiv · 10.1101/2025.02.11.637337

An artificial metal-free peroxidase designed using a ferritin cage

Tian, J.·Maity, B.·Furuta, T.·Pan, T.·Ueno, T.
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Abstract

Developing artificial enzymes is challenging because it requires precise design of active sites with well-arranged amino acid residues. Histidine-rich oligopeptides have been recently shown to exhibit peroxidase-mimetic activities, but their catalytic function relies on maintaining unique supramolecular structures. This work demonstrates the design of a specific array of histidine residues on the internal surface of the ferritin cage to function as an active center for catalysis. The crystal structures of the ferritin mutants revealed histidine-histidine interactions, forming well-defined histidine clusters (His-clusters). These mutants exhibit peroxidase-mimetic activities by oxidizing 3,3,5, 5-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide. Molecular dynamics simulations further highlight the co-localization of TMB and hydrogen peroxide at the histidine-rich clusters, indicating that the confined environment of the ferritin cage enhances their interactions. This study presents a simple yet effective approach to design cofactor-free artificial enzymes, paving the way for innovations in bioinspired catalysis.

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Tian, J., Maity, B., Furuta, T., Pan, T., Ueno, T.. 2025-02-12. An artificial metal-free peroxidase designed using a ferritin cage. https://doi.org/10.1101/2025.02.11.637337

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