This project addressed significant global challenges in catalysis for energy and sustainable chemistry via learning from, and exploiting, nature’s enzyme catalysts. Metal-containing enzymes within microorganisms catalyse the transformation of carbon dioxide into simple carbon building blocks or fuels, the reduction of dinitrogen to ammonia under ambient conditions and the production and utilisation of dihydrogen. Catalytic sites for these reactions within the enzymes are necessarily based on metals that are abundant in the environment, including iron, nickel and molybdenum. However, attempts to generate biomimetic catalysts have largely failed to reproduce the high activity, stability and selectivity of enzymes. One important key to the exquisite catalysis of enzymes is the choreography of proton and electron transfer and substrate binding during catalytic turnover, and this project set out to establish and utilise a suite of spectroscopic and structural techniques to understand proton-coupled electron transfer and how this is timed with substrate binding and transformation in enzymes.
Key objectives of the action were (i) to establish operando techniques which can be used to understand the intricately controlled chemistry of enzymes; (ii) to apply these to hydrogenases to see what catalytic lessons we can glean from understanding how hydrogen gas is activated cleanly in biology, and how we can exploit hydrogenases themselves in cleaner chemical production; (iii) to apply similar approaches to nitrogenase to understand how natural nitrogen fixation to ammonia can be conducted under ambient conditions in contrast to the high temperature/pressure Haber Bosch process; (iv) to understand the selectivity and efficiency of biological CO2 reduction; and (v) to disseminate these lessons to the wider catalysis community to contribution new catalyst design principles.
The project successfully established operando techniques which will be valuable across structural enzymology, and which have revealed steps in metalloenzyme catalysis. Using a combination of electrochemistry to poise protein crystals in defined redox states, and infrared microspectroscopy and EPR spectroscopy to verify redox state, we were able to record x-ray diffraction structures of metalloenzymes including hydrogenase and nitrogenase in redox states relevant to catalysis. We have gained insight into proton-coupled electron transfer steps, such as the role of subtle movement in a glutamate side change in the mechanism of NiFe hydrogenase. These findings contribute new insight for the design of catalysts for energy technologies for clean, sustainable fuel production and fuel cells, and more energy-economical industrial chemical processes. We have also discovered new ways of harnessing hydrogenase enzymes for hydrogenation reactions under mild conditions, including the hydrogenation of nitro-compounds, and of flavins for coupling to various biocatalytic reductions. This opens up cleaner, simpler biocatalysis for chemical manufacturing, particularly for pharmaceuticals and other fine chemicals. We have disseminated these findings to the research community via a wide array of conference talks and publications. Overall, the findings of the project benefit society by contributing to the urgent challenges posed by global climate change and energy/climate inequality, including cleaner chemical manufacturing, and the need for catalysis for hydrogen cycling and ammonia synthesis.
