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Title: Molecular basis of polyketide β-methyl branch formation
Author: Nair, Asha V.
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2013
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Type I modular polyketide synthases (PKSs) are giant multi-functional enzymes that catalyse the assembly of a range of bioactive natural products. The bacillaene synthase (PksX) from Bacillus subtilis is a member of the trans-A T PKS family and is responsible for the biosynthesis of the broad-spectrum antibiotic bacillaene. As in other trans-A T synthases the bacillaene system employs a five enzyme "RCS cassette" to introduce a distinctive ft-methyl branch into the final functional product. In this thesis I describe the structural and functional characterisation of three of the bacillaene synthase RCS cassette enzymes PksG, PksR and Pksl. These enzymes are responsible for the final three steps in ft-methyl branch formation in the bacillaene pathway and have been characterised using a combination of macromolecular X-ray crystallography, molecular biology and enzymological approaches. These studies not only provide significant insight into the formation of β-methyl branches during polyketide biosynthesis, but also reveal new routes towards the exploitation of this unique biosynthetic activity for the derivatisation of natural product based pharmaceutical/agrochemical agents.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available