We have examined the rapid reaction kinetics and spectroscopic properties of the molybdenum-containing, NAD+-dependent FdsABG formate dehydrogenase from C. necator, demonstrating the direct transfer of the substrate Ca hydrogen to the molybdenum center of the enzyme in the course of the reaction. In light of recent advances in our understanding of the structure of the molybdenum center propose a reaction mechanism involving direct hydride transfer from formate to a Mo=S group of the molybdenum center . We have also examined the ability of the enzyme to catalyze the reverse of the physiological reaction, the reduction of CO2 to formate utilizing NADH as electron donor. Contrary to previous studies, we find that it is in fact effective in catalyzing the reverse reaction, with a kcat of 10 s-1. We also quantify the stoichiometric accumulation of formic acid as the product of the reaction and demonstrate that the observed kinetic parameters for catalysis in the forward and reverse reaction are thermodynamically consistent, complying with the First Law of Thermodynamics. Finally, we demonstrate the reaction conditions necessary for gauging the ability of a given formate dehydrogenase or other CO2 -utilizing enzyme to catalyze the reverse direction so as to avoid false negative results. We conclude that all molybdenum- and tungsten-containing formate dehydrogenases and related enzymes likely operate via a simple hydride transfer mechanism and are effective in catalyzing the reversible interconversion of CO2 and formate under the appropriate experimental conditions .
 Niks, D, Duvvuru, J., Escalona, M. & Hille, R. (2016) Spectrosccopic and kinetic characterization of the soluble, NAD+-dependent formate dehydrogenase from Ralstonia eutropha, J. Biol. Chem. 291, 1162-1174.
 Yu, X., Niks, D., Mulchandani, A., & Hille, R. Efficient reduction of CO2 by the molybdenum-containing formate dehydrogenase from Cupriavidus necator. J. Biol. Chem. 292, 16872-16879.