Work

An unexpected alternative viologen electron mediator site in tungsten‐containing formate dehydrogenase

Year: 2026

Type: article

Abstract: The molecular mechanisms by which artificial electron mediators, such as ethyl viologen (EV), interact with tungsten‐containing formate dehydrogenases (FDHs) during reversible CO 2 reduction remain poorly understood. Here, we reveal an unexpected alternative mediator interaction site in FDH1 of Methylorubrum extorquens AM1. Removing the native flavin mononucleotide cofactor abolishes NAD + ‐dependent activity but preserves EV‐driven catalysis. Through mutagenesis, kinetic analysis, and molecular docking, we identified a cooperative aromatic network—comprising residues F232, F471, and Y329—that stabilizes EV via stacking interactions near the proximal B1 iron–sulfur cluster. Disrupting these residues impairs EV‐mediated electron transfer without destabilizing global structure. These findings reveal a dual interaction strategy for artificial mediators in tungsten FDHs, offering a structural framework to rationally engineer biocatalysts for CO 2 conversion.

Source: FEBS Letters

DOI: 10.1002/1873-3468.70373

Authors: Eleni G. Poloniataki, Yong Hwan Kim

Institution: Ulsan National Institute of Science and Technology

Language: English

Topic: Metalloenzymes and iron-sulfur proteins

Subfield: Renewable Energy, Sustainability and the Environment

Field: Energy

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $3,980

Funder: National Research Foundation of Korea