Oral Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Breaking it All Down: Formate Oxidation, CO2 Reduction and NADH/NAD+ Turnover in Formate Dehydrogenase (120541)

Paul V Bernhardt 1
  1. University of Queensland, Brisbane, QLD, Australia

Coupling an oxidoreductase enzyme with an electrochemical working electrode is the foundation of electrochemical biosensors and for electrochemically driven biotransformations. The intrinsic substrate selectivity of an enzyme may be exploited to generate a system that can work effectively in complex mixtures of compounds. 

We have been particularly interested in electron transfer reactions and electrochemistry of the mononuclear molybdenum enzyme superfamily that includes both oxidases/dehydrogenases and reductases which generally mediate 2-electron O-atom transfer reactions of a variety of substrates both organic and inorganic:

Mo(IV)=O  + Z ⇔ Mo(IV) + ZO 

One of the most complex Mo enzymes of all is the bacterial formate dehydrogenase FdsDABG from Cupriavidus necator which comprises 7 Fe/S clusters and an FMN cofactor which act as electron relays during oxidation of formate to CO2 at the Mo active site. FdsDABG may also run in reverse by reducing CO2 to formate. This presentation will include some of our recent findings from this interesting enzyme including analysis of its various subunits and the roles that they play in catalysis. 

 

 

  1. Kalimuthu, P.; Bernhardt, P. V. Electrochemistry of molybdenum and tungsten enzymes. In Molybdenum and Tungsten Enzymes, RSC Metallobiology, Vol. 7; Royal Society of Chemistry, 2017; pp 168-222.
  2. Harmer, J. R.; Hakopian, S.; Niks, D.; Hille, R.; Bernhardt, P. V. Redox Characterization of the Complex Molybdenum Enzyme Formate Dehydrogenase from Cupriavidus necator. J. Am. Chem. Soc. 2023, 145 (47), 25850-25863