Towards a photocatalytic carboxylase

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Illumination is able to unlock a wide range of photochemical reactions, but light is rarely used by living organisms. In fact, to date only three light dependent enzymes have been described in detail. Nevertheless, there is considerable scope for such reactions, given that a range of biological cofactors (such as nicotinamide or flavins) undergo photoredox chemistry under appropriate conditions. Indeed, several groups recently reported the discovery of light-dependent non-natural reactivity with a range of cofactor binding enzymes (1). We seek to develop novel light-dependent enzymes to improve our understanding of how the enzyme protein matrix directs photochemistry, and to use CO2 as a building block. Our immediate targets are carboxylation reactions of interest to support sustainable production of carboxylic acids of interest, inspired by synthetic photochemistry. Making use of a considerable library of flavin-dependent enzymes at the Manchester Institute for Biotechnology (MIB; references 1-2), we will use (rational) enzyme evolution to generate non-natural light-dependent carboxylases with appropriate substrate specificity. The PhD student will be based in Department of Chemistry and the Manchester Institute of Biotechnology (MIB) and will be co-supervised by Professor David Leys (structural biology), Professor Sam Hay (computational chemistry) and Professor Anthony Green (enzyme evolution) in collaboration with our industrial sponsor Shell. The project is interdisciplinary, giving the student the opportunity to gain broad experience in modern experimental biophysics, enzymology, biocatalysis and structural biology alongside biochemically-relevant computational chemistry within an industrially relevant setting.