Repurposing of protein nanopores as artificial transmembrane enzymes

标题：蛋白质纳米孔作为人工跨膜酶的再利用项目摘要：该项目寻求使用生物结合化学将非天然的、合成的催化功能结合到跨越膜的生物孔蛋白中。虽然天然蛋白质缺乏任何催化活性，但目标重新设计的跨膜蛋白质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，并结合Jarvis小组在人工酶设计方面的专业知识。单通道电生理学将使反应机制能够在单分子水平上进行监测。一旦开发出工作系统并在单分子水平上进行表征，最终目标将是赋予脂膜大量蛋白质，以实现可转化为可用于工业生物技术的流动反应器的制备规模的跨膜化学转化。该项目将涉及使用膜片钳技术的计算蛋白质设计、合成化学、生物结合化学、生物/化学催化和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.