Direct detection of a single [4Fe‐4S] cluster in a tungsten‐containing enzyme: Electrochemical conversion of CO₂ into formate by formate dehydrogenase

Abstract The conversion of CO₂ into fuels and valuable chemicals is one of the central topics to combat climate change and meet the growing demand for renewable energy. Herein, we show that the formate dehydrogenase from Clostridium ljungdahlii (ClFDH) adsorbed on electrodes displays clear characteristic voltammetric signals that can be assigned to the reduction and oxidation potential of the [4Fe‐4S]^2+/+ cluster under nonturnover conditions. Upon adding substrates, the signals transform into a specific redox center that engages in catalytic electron transport. ClFDH catalyzes rapid and efficient reversible interconversion between CO₂ and formate in the presence of substrates. The turnover frequency of electrochemical CO₂ reduction is determined as 1210 s⁻¹ at 25 °C and pH 7.0, which can be further enhanced up to 1786 s⁻¹ at 50°C. The Faradaic efficiency at −0.6 V (vs. standard hydrogen electrode) is recorded as 99.3% in a 2‐h reaction. Inhibition experiments and theoretical modeling disclose interesting pathways for CO₂ entry, formate exit, and OCN⁻ competition, suggesting an oxidation‐state‐dependent binding mechanism of catalysis. Our results provide a different perspective for understanding the catalytic mechanism of FDH and original insights into the design of synthetic catalysts.