Repurposing of protein nanopores as artificial transmembrane enzymes

项目概述：本项目旨在利用生物偶联化学将非天然的合成催化功能整合到跨膜生物孔蛋白中。当天然蛋白缺乏任何催化活性时，靶向重组的跨膜蛋白将能够在分子跨膜运输时催化反应。该项目将利用Cockroft集团最近开发的原位跨膜蛋白质修饰化学技术，并结合Jarvis集团在人工酶设计方面的专业知识。单通道电生理学将能够在单分子水平上监测反应机制。一旦一个工作系统被开发出来并在单分子水平上进行表征，最终的目标将是赋予脂质膜大量的蛋白质，以实现制备规模的跨膜化学转化，这种化学转化可以转化为流动反应器，用于工业生物技术。该项目将涉及计算蛋白设计、合成化学、生物偶联化学、生物/化学催化和使用膜片钳技术的跨膜记录方面的培训。

Title: Repurposing of protein nanopores as artificial transmembrane enzymesProject Summary:This project seeks to use bioconjugation chemistry to incorporate non-native, synthetic catalytic functionalities into membrane-spanning biological pore proteins. While the native protein lacks any catalytic activity, the targeted re-engineered transmembrane proteins will be capable of catalysing reactions as molecules are transported across a membrane.The project will exploit in situ transmembrane protein modification chemistry recently developed within the Cockroft group in combination with expertise of the Jarvis group in the design of artificial enzymes. Single-channel electrophysiology will enable reaction mechanisms to be monitored on the single-molecule level. Once a working system has been developed and characterised at the single-molecule level, the ultimate aim will be to endow lipid membranes with large numbers of proteins to enable preparative-scale transmembrane chemical transformations that could be translated into flow reactors thatcould be exploited in industrial biotechnology.The project will involve training in computational protein design, synthetic chemistry, bioconjugation chemistry, bio/chemical catalysis and transmembrane recordings using the patch clamp technique.