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 group1 in combination with expertise of the Jarvis group in the design of artificial enzymes.2 Single-channel electrophysiology will enable reaction mechanisms to be monitored on the single-molecule level.3 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 that could 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.
1. In situ synthetic functionalization of a transmembrane protein nanopore, S. Borsley, S. L. Cockroft, ACS Nano, 12, 786-794.
2. Enzyme activity by design: an artificial rhodium hydroformylase for linear aldehydes, A. G. Jarvis, L. Obrecht, P. J. Deuss, W. Laan, E. K. Gibson, P. P. Wells, and P. C. J. Kamer, Angew. Chem., Int. Ed. 2017, 56, 13596-13600 (VIP paper).
3. Synthetically functionalized protein nanopores: enabling single-molecule observation of the CuAAC reaction mechanism, M. Haugland, S. Borsley, S. L. Cockroft, submitted.
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