Project No.2339

PRIORITY PROJECT

Primary Supervisor

Dr Bruce Lichtenstein – University of Portsmouth

Co-Supervisor(s)

Professor Martin Warren – University of Kent

Prof Ross Anderson – University of Bristol

Summary

Nature wields incredible control over chemistry by using protein structures to tweak the activities of amino acids and catalytic cofactors.

In some cases, proteins manipulate the function of cofactors to incredible degrees: vitamin B12, for instance, is used by nature to transfer methyl groups, initiate rearrangement reactions, and breakdown of halogenated substrates. In this project, we seek to understand how nature manages the flexible chemistry of vitamin B12, and related metallocorrin cofactors, by designing de novo proteins to bind to them and manipulate their function. By building corrin-dependent enzymes from the ground up, we will be able to define the natural engineering principles that govern their properties, growing our understanding of how natural proteins work and giving unique insights into how to construct B12-dependent enzymes for bespoke purposes. This new knowledge will have applications in everything from biosensing to the development of novel industrial biocatalysts founded on the incredible properties of metallocorrins.

In this project, the student will work as part of a multi-institutional team focused on engineering de novo designed proteins to reveal the rules that govern their function and build new protein based bioelectronics. This will provide the student with immediate access and support from a broad team with relevant expertise beyond the core supervisory team.

This project would be ideal for a student with a masters in biochemistry, chemistry, or related subjects, with experience in protein expression or chemical synthesis, who is interested in learning how to build proteins from scratch using computational and manual approaches.