Towards vibrational control of enzymes for biotechnology and biocatalysis

The vast majority of biological reactions are catalysed by enzymes, which often exhibit exquisite selectivity and massive catalytic rate enhancements. With advances in enzyme engineering and an increasing desire for more sustainable synthesis, enzyme-mediated biocatalysis is becoming an established alternative to traditional methods of both commodity and high-value chemical production. In many cases, it would be desirable to have a rapid and real-time method of tuning enzyme activity, e.g. to control flux through a multi-enzyme cascade or in vivo metabolic pathway. One possibility is through direct vibrational control of the enzyme reaction.

Chemical reactions typically involve the making and breaking of bonds, which are accompanied by changes in molecular vibrations of the reactants and surrounding environment, so it is possible to alter the rate of reaction through excitation of promoting or demoting vibrational modes. In condensed matter (proteins, surfaces, etc) energy from excited molecular vibrations is expected to dissipate in picoseconds, making continuous excitation impossible due to resulting sample heating. Recent advances in ultrafast laser spectroscopy allows a solution - It is now becoming practical to directly excite molecular vibrations using ultrafast (sub-picosecond) pulses of infrared (IR) light, which can lead to significant rate enhancements of thermal reactions in the gas-phase and on surfaces without excessive heating. This project now aims to extend and develop this methodology, using ultrafast IR light pulses to control the rate of enzyme reactions.

This work will involve instrument and method development alongside new data analysis and experimental design procedures. Computational chemistry (MD simulations and/or DFT modelling) will be used to aid in experimental design and interpretation of results. Ultimately, we will aim to design and test a new ultrafast laser-controlled bioreactor. The project falls within the remit of both 'technologies and methodological development' and 'industrial biotechnology' and is firmly embedded at the interface of chemistry, biology and physics, a key driver for BBSRC in the 'Exploiting new ways of working' agenda. It draws on key bioscience skills, including new areas of applicable to bioscience (e.g. protein engineering, dynamic structural science) and state-of-the-art time resolved spectroscopy approaches. These are 'at risk' skills in the UK landscape and training in these areas is therefore vital to ensure a balanced and knowledgeable talent pool is maintained in the UK biosciences. Overall, the work will provide a highly interdisciplinary approach to (bio)chemistry/ biophysics-based research, offering highly diverse training opportunities to a PhD student, who will have the additional benefit of being able to access the supervisors' laboratories on a daily basis, as they are all co-located within the same building (MIB).