Evolution of quantum effects in enzymes

Hydrogen-transfer reactions involving hydride, hydrogen atom or proton transfers are ubiquitous in enzyme-catalysed reactions. It is now well established that these reactions can occur via a mechanism involving some degree of quantum mechanical tunnelling (QMT), and thus are a feature of quantum biology. The QMT contribution is highly variable and is thought to correlate with kinetic isotope effects (KIEs) measured on these reactions typically with hydrogen and deuterium.

An open question remains whether there has been evolutionary pressure to select for quantum mechanical phenomena such as QMT during enzyme catalysis. Theoretically, it is possible to increase the rate of an enzyme-catalysed H-transfer reaction by increasing the tunnelling contribution, so this could offer a fitness advantage. However, typical strategies to increase the tunnelling contribution are also likely to increase the rate of classical (over-the-barrier) H-transfer.

In this project we aim to combine experimental studies of H-tunnelling in enzyme catalysed reactions with laboratory/ directed evolution (DE) and computational chemistry. DE will be performed on enzyme(s) that utilise rate-limiting H-transfers during their catalytic mechanism. High- and medium-throughput screening methods that select for enzyme activity with both protiated and deuterated substrates will be used in order to allow parallel evolution of enzymes evolved specifically for H- and D- transfer.

This will allow a new and more comprehensive approach to the exploration of the relationships between H- and D- transfer kinetics and QMT during enzyme evolution and will also establish whether selecting for improved D-transfer kinetics provides new avenues for improving enzyme performance, e.g. for improvement of industrial biocatalysts.