Leicester Institute of Structural and Chemical Biology

Philip Ash

Metalloenzyme mechanism with sub-turnover frequency time resolution

Research summary

The activation and redox chemistry of small molecules such as CO, CO2, H2, formate, O2, NO, N2, and NH3 by metalloenzymes play important roles in vital processes such as the global carbon and nitrogen cycles, and as sources of energy or low-potential reducing equivalents in cellular environments (for example certain bacteria have evolved to use CO2 as their sole carbon source and H2 as their sole energy source). Despite the current urgent need for sustainable fuels and greener routes to chemical synthesis, detailed mechanistic understanding of how these small molecule activation reactions are carried out in nature is often lacking. In part this is due to the high turnover frequencies achieved by metalloenzymes, which are often capable of activating small molecules at rates of several thousand reactions every second. New methods are therefore required that are capable of probing metalloenzyme mechanism on fast timescales, or else the native reaction must be retarded to allow kinetic study by more conventional methods.


The active sites of redox metalloenzymes are often based around an inorganic core and share compositional and structural similarities with naturally-occurring minerals. As such they are well-suited to study using ‘standard’ spectroscopic methods such as infrared, Raman, and X-ray spectroscopies. Electrochemistry provides convenient control over redox state, and makes it possible to ‘trap’ metalloenzymes in inactive or ‘resting’ states ready for spectroscopic study. I am developing methods that combine this electrochemical control with fast experimental triggers to initiate reactivity, and fast spectroscopic methods to allow investigation of metalloenzyme mechanism with sub-turnover frequency time resolution. A deeper mechanistic understanding of how nature has developed efficient metalloenzymes should provide inspiration for the next generation of biomimetic catalysts for ‘green’ energy and synthesis.

Key publications

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