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Title: Proteopolymersome : a versatile tool to study microsomal monooxygenases and for drug screening
Author: Omar Ali, Hossam Eldin
ISNI:       0000 0004 7231 1545
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2018
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Microsomal monooxygenases are one of the most important subfamilies of cytochrome P450 enzymes. These membrane-associated enzymes, and their reductases, are of high research importance for the role they play in drug metabolism and interactions. One of the most active member of this family of enzymes is the cytochrome P450 3A4 enzyme, which metabolises over half of all current drugs available on the market. Being able to study and understand how this enzyme works is important for future drug development, including the creation of novel targets and predicting possible side effects. The creation of a functional CYP3A4 enzyme model with biological fidelity has been the goal of many research groups. However, challenges have been faced in the development of such models, both in creation of a stable and bio-compatible membrane environment for the anchoring of the enzymes, as well as having sufficient enzyme activity. Here we present a system created using cell-free expression system supplemented with polymer vesicles, so called polymersomes, for simple and quick co-expression of cytochrome P450 3A4, cytochrome P450 reductase and cytochrome b5. The availability of polymersome in the expression mixture allowed for the co-insertion of the enzymes into the polymersome membranes. The resultant proteopolymersomes were readily purified, and analysis showed them to be active and stable while maintaining the structural integrity of the polymersome throughout the entire process. This developed system has a high value in pharmaceutical research and is not only applicable to other members of the microsomal monooxygenase family of enzymes, but also to all other high interest membrane associated enzymes.
Supervisor: Wong, Tuck ; Nallani, Madhavan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available