Investigation of polyprenyl and dolichyl phosphomannose synthase enzymes as biocatalysts and as targets for drug discovery

Lead Research Organisation: University of Warwick
Department Name: Chemistry

Abstract

Enzymes will be expressed and purified to investigate the bioactivity with unnatural substrates synthesised in the lab. Directed evolution will be performed to improve enzyme properties as biocatalysts. Besides, enzymes and mutants structure will be investigated by NMR and X-ray crystallography as potential target for the development of novel therapeutics.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509796/1 01/10/2016 30/09/2021
1938885 Studentship EP/N509796/1 02/10/2017 30/09/2021 Scott Llywellyn Andrew
 
Description A variety of non-natural phospholipids have been synthesised; both polyprenyl and mycoketide mimics have been synthesised.
They have been tested alongside natural phospholipids with two enzymes. In general, the synthetic substrates are processed by the enzymes, albeit to a lesser degree than the natural substrates.
A sulpholipid analogue has been synthesised and tested, however found to be inactive as a substrate and as an inhibitor.
A GDP recycling system has been designed, and two enzymes have been cloned and expressed for use in the system.
Exploitation Route They have laid the foundations for synthesis of novel mannosyl phospholipids, which might be synthesised in high yields. These can be used to study glycosyltransferases in greater detail, and antigen responses in Mycobacterium spp.
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology