Towards a photocatalytic carboxylase

光催化羧化酶的研究

• 批准号: 2777718
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2777718
• 关键词: Towards; photocatalytic; carboxylase

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.

照明能够解锁一系列的光化学反应，但光很少被生物利用。事实上，到目前为止，只有三种依赖于光的酶被详细描述。然而，考虑到一系列生物辅因子(如烟酰胺或黄素)在适当的条件下经历光氧化还原化学，此类反应仍有相当大的空间。事实上，几个小组最近报告发现了与一系列辅因子结合酶的光依赖的非自然反应(1)。我们寻求开发新型的光依赖酶，以提高我们对酶蛋白基质如何指导光化学的理解，并利用二氧化碳作为构建块。我们的直接目标是在合成光化学的启发下，进行感兴趣的羧化反应，以支持感兴趣的羧酸的可持续生产。利用曼彻斯特生物技术研究所(MIB；参考文献1-2)相当多的黄素依赖酶文库，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的羧基酶。这名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David Leys教授(结构生物学)、Sam Hay教授(计算化学)和Anthony Green教授(酶进化)与我们的工业赞助商壳牌合作共同指导。该项目是跨学科的，使学生有机会在与工业相关的环境中获得现代实验生物物理学、酶学、生物催化和结构生物学以及与生物化学相关的计算化学方面的广泛经验。