Hydrogenase reengineering – HYDRE

Hydrogenases are the enzymes that oxidize or produce H2 at a NiFe or FeFe active site. The principles of their active site mechanisms have been understood by combining a number of techniques over decades of investigations by the international scientific community, including the partners of this project. This knowledge is now crucial to help chemists produce the solar-fuel catalysts that we need to mitigate global warming and to reduce our dependence on fossil fuels. However, hydrogenases are very diverse in terms of structures and catalytic properties, and to become able to make more useful catalysts, one needs to understand what gives certain hydrogenases the properties that are particularly sought after: high turnover frequencies in either direction of the reaction in response to even a small departure from thermodynamic equilibrium (i.e., at small overpotential), and preference for the reaction with H2 over O2 when the catalyst must operate in air. This goal is now within reach, because the partners of the project have set the methods that can be used to produce and compare original enzymes, study them using advanced kinetic techniques, and re-engineer them with the goal of transferring certain catalytic properties between homologous enzymes. This project will combine the expertise of the three partners in biophysics (notably electrochemical kinetics), protein engineering and structural biology to produce and study very original hydrogenases. Identifying the structural features that confer useful natural catalytic properties to enzymes and understanding the molecular mechanisms by which this occurs will give invaluable knowledge about how ideal catalysts work, and how to improve synthetic catalysts.