Abstract
Bioelectrocatalytic CO2 reduction offers a sustainable route for CO2 bioconversion, yet remains limited by interfacial-intramolecular electron transfer and oxygen sensitivity. Here, we mine a formate dehydrogenase from Shewanella oneidensis MR-1 (SoFdhAB) featuring completely oxygen tolerant and direct-electron-transfer (DET) electrocatalytic performances. Cryo-electron microscopy (Cryo-EM) analysis reveals an intramolecular electron highway comprising five [4Fe-4S] clusters, a regional face-face contact facilitating interfacial ET, and a unique oxygen resistance mechanism different from inactivation-activation. By acquiring a beneficial variant SoFdhAB-Y94S, a direct bioelectrocatalytic CO2 reduction system is constructed, accumulating 2.88 ± 0.03 mmol formate in 64 hours with a steady rate of 45.3 ± 0.5 μmol h−1 cm−2 and a Faradaic efficiency of 93.1 ± 5.2%. The merits of oxygen tolerance and efficient (electro)catalytic property endow SoFdhAB a robust enzyme adopted in potential application scenarios, and the inherent DET capability may inspire the interfacial engineering of other oxidoreductases.
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Data availability
The structural model of SoFdhAB has been deposited in the Protein Data Bank (PDB) with accession codes 9VAP. Protein structures of EcFDH-H, PDB ID 1FDI, TkHDCR, PDB ID 7QV7 and DvH-FDH, PDB ID 6SDR are available from the PDB. The genomic data of Shewanella oneidensis MR-1 are available from the National Center for Biotechnology Information (NCBI) database [https://www.ncbi.nlm.nih.gov/nuccore/AE014299.2]. All relevant data generated and analyzed during this study which include enzyme activity assay and electrochemical data are included in this article and its supplementary information. Source data are provided with this paper.
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Acknowledgements
This study was supported by Strategic Priority Research Program of the Chinese Academy of Sciences (XDC0120103 to L. Z.), Coal-Major Project (2025ZD1701600 to L. Z.), the Tianjin Science Fund for Distinguished Young Scholars (22JCJQJC00100 to Z. Z.), and the International Partnership Program of Chinese Academy of Sciences, Grant No. 306GJHZ2025003BS to L. Z. We are grateful to Professor Shenghai Chang for his supervision in structural analysis, and to Dr. Tailin Wang for insightful discussions.
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Experiment, data analysis and writing the initial manuscript were performed by W.L. P.Z. preformed the bioinformatics analysis. Molecular dynamics (MD) simulation was performed by X.W. and H.C. (Haiyang Cui) provided supervision. Cryo-EM analysis was supervised by K.Z., W.Y., and C.Y. Electrochemical experiments were supervised by H.C. (Huijuan Cui) Data analysis and biochemistry experiments were supervised by C.Y., Z.Z., and J.S. J.L. provide experimental materials. Project conception, fund support, overall supervision and writing paper were performed by L.Z.
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Liu, W., Zhang, P., Wang, X. et al. An interfacial-intramolecular electron highway for accelerated electrocatalytic CO2 reduction by an O2-tolerant formate dehydrogenase. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69827-w
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DOI: https://doi.org/10.1038/s41467-026-69827-w
