MeCO2Bio

CO dehydrogenases (CODH) are metalloenzymes that catalyze the reversible reduction of CO2 to CO at very high rates, small overpotentials and with a very high specificity regarding the product of the reaction (only CO is formed, not formate nor oxalate). They are invaluable inspiration sources for designing efficient catalysts for the reduction of CO2, which we will need to decrease atmospheric CO2 levels. CODHs catalyze the reduction of CO2 at a NiFe4S4 inorganic active site, and the electrons needed for the reaction are transported from the redox partner along a series of FeS clusters. To date, only a small number of homologous CODHs have been studied, and we have indications that these enzymes are not representative of the diversity of the catalytic properties of this family of enzymes. Indeed, we have recently shown that the previously uncharacterized CODH from Desulfovibrio vulgaris (Dv) differs significantly from the other ones in several ways: for instance, the clusters acting as electron relays are atypical, and this enzyme is surprisingly resistant to the inhibitor O2. In this interdisciplinary project, we want to explore the biodiversity of CODHs, by purifying and characterizing the properties of CODHs from a large variety of microorganisms (archaea, bacteria, thermophiles, strict anaerobes, sulfate reducers, strict aerobes). We think that the variety of growth conditions of these organisms will translate into a diversity of properties of their CODHs. We will use protein film voltammetry (Fourmond et al, Curr. Op. Electrochem 2017) to characterize various aspect of their reactivity: their mechanism, the role of the FeS clusters acting as electron relays, the substrate channel(s), the reactivity with O2 and other inhibitors. By the quantitative comparison of the properties of the different CODHs, which we will combine with new structural information, we will understand the molecular determinants of the reactivity of CODHs, and the reasons why they are such excellent catalysts.