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

点击翻译按钮获取中文摘要

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.