Non-native Photobiocatalysis: Using Non-Natural Single Electron Transfer Reactions to Enable the Enantioselective Synthesis of Amines

第一年：CDT所有一年级学生成员的通用培训活动。第二年至第四年：酶是不对称合成的有吸引力的催化剂，因为它们具有超过传统化学方法的选择性和效率，同时还具有独特的优化模式，允许通过蛋白质工程针对特定的底物和选择性结果定制其化学结构。然而，酶催化的应用通常局限于自然界中的反应。最近，利用天然酶中的非自然反应机制已成为扩大生物催化合成体系的一种有吸引力的策略，并有可能解决化学合成中许多长期存在的选择性和反应性挑战。本项目将对在亚胺还原酶(IRED)中进行非自然单电子转移反应以实现烷基胺的光生物催化不对称合成的可行性进行初步探索。在微摩尔尺度上准确测定粗制反应混合物的对映体选择性仍然是一个持续的挑战。我们希望最终开发出一种强大的高通量方法来生成标准化的数据集，这将通过将序列与活性联系起来促进未来的酶优化。

Year 1: Generic training activities for all first-year student members of the CDT.Year 2-4: Enzymes are attractive catalysts for asymmetric synthesis as they enable selectivities and efficiencies that surpass those of conventional chemical methods while also possessing a unique mode of optimisation, allowing their chemical structures to be tailored towards a specific substrate and selectivity outcomes, via protein engineering. However, the applications of enzymatic catalysis have been generally restricted to reactions found in nature. Recently, exploiting non-natural reaction mechanisms within native enzymes has emerged as an attractive strategy for expanding the synthetic repertoire of biocatalysis and has the potential to address many long-standing selectivity and reactivity challenges in chemical synthesis. This project will carry out an initial exploration into the viability of conducting non-natural single electron transfer reactions within imine reductases (IREDs) to enable the photo-biocatalytic asymmetric synthesis of alkyl amines. Accurate determination of enantioselectivity from crude reaction mixtures on a micromolar scale remains an ongoing challenge. We hope the eventual development of a robust high-throughput methodology to generate standardised datasets will facilitate future enzymatic optimisation through linking sequence to activity.