Modernising Electrochemical Enzymology to Map Electron Transfer (Enzyme e-map)

In Nature the production of hydrogen and methane fuel molecules from readily available starting materials such as water and carbon dioxide is achieved selectively, efficiently and rapidly by electrocatalytic redox-metalloenzymes containing non-precious transition metal active sites.  

The outstanding recent scientific advances made in molecular biology have made the development of biofuel technologies based on these enzymes a reality, but such applications require a complementary toolkit of physical chemistry methods that can dissect how DNA sequence and protein structure relates to function.  

Classic bio-electrochemistry methods developed in the 1980s have been a powerful way to probe the active site reactivity of such enzymes, but they have been unable to map the electron transfer processes which underpin the catalysis. Therefore, we have been limited to a narrowly active-site focussed view of enzyme mechanism.  

This project will transform the state of the art in bio-electrochemistry to deliver a powerful new technique that can “see” the electron-transfer processes of the highly evolved and essential electron-transfer reaction centres in redox-enzymes, and deconvolute their role in electrocatalysis.  

This will be achieved by deploying advanced computational methods to integrate intelligent experimental design into electrochemistry to develop a methodology that enables the separation and accurate modelling of the electron transfer processes of an enzyme bound to substrate, and chemical biology methods to develop linker molecules for light-activated electrografting of proteins and enzymes onto electrodes.  

The project will showcase the power of this new electrochemical enzymology toolkit by conducting previously impossible hypothesis-led investigations and enzyme-discovery projects into i) cellulose-degrading LPMOs that play a crucial role in biorefinery enzyme cocktails and ii) hydrogenases, Ni+Fe or Fe-only metalloenzymes that are as rapid and efficient at hydrogen-catalysis as platinum. 

The project is a collaboration with the University of York (lead).