Towards a photocatalytic carboxylase

照明能够解锁广泛的光化学反应，但光很少被生物体使用。事实上，迄今为止只有三种光依赖性酶被详细描述。然而，考虑到一系列生物辅因子（如烟酰胺或黄素）在适当条件下经历光氧化还原化学，这种反应有相当大的范围。事实上，最近有几个研究小组报告发现了一系列辅因子结合酶的光依赖性非天然反应性（1）。我们寻求开发新的光依赖性酶，以提高我们对酶蛋白基质如何指导光化学的理解，并使用CO2作为构建模块。我们的直接目标是感兴趣的羧化反应，以支持感兴趣的羧酸的可持续生产，灵感来自合成光化学。利用曼彻斯特生物技术研究所（MIB;参考文献1-2）的大量黄素依赖性酶库，我们将使用（合理的）酶进化来产生具有适当底物特异性的非自然光依赖性羧化酶。该博士生将在化学系和曼彻斯特生物技术研究所（MIB）工作，并将由大卫·莱斯教授（结构生物学）、萨姆·海伊教授（计算化学）和安东尼·绿色教授（酶进化）与我们的工业赞助商壳牌公司合作共同监督。该项目是跨学科的，让学生有机会在现代实验生物物理学，酶学，生物催化和结构生物学以及工业相关环境中的生物化学相关计算化学方面获得广泛的经验。

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.