Studies on the biosynthesis of antibiotics mupirocin and thiomarinol

Yadav, Mukul (2017). Studies on the biosynthesis of antibiotics mupirocin and thiomarinol. University of Birmingham. Ph.D.

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Abstract

Biosynthetic steps in the mupirocin (pseudomonic acids) biosynthetic pathway of \(Pseudomonas\) \(fluorescens\) NCIMB 10586 have already been deduced. Putative functions of most of the genes of \(mup\) cluster have been assigned although exact sequence of steps in the pathway and their timings are not yet known. Thiomarinols are another group of anti-bacterials produced by \(Pseudoalteromonas\) \(sp\). SANK 73390. Very little is known about the biosynthesis of thiomarinols that share striking structural similarity with pseudomonic acids in their polyketide and fatty acid moieties. This similarity is reflected at genetic level as significant similarity in amino acid identity between the products of at least 27 ORFs in these biosynthetic clusters.

This project aimed to learn more of biosynthetic steps in the biosynthesis of mupirocin and thiomarinol antibiotics by testing for functional cross-complementation between pair of genes or a group of genes whose products show significant homology. Surprisingly, only two genes \(tmlJ\) and \(tmlS\) out of nine studied showed complementation in the \(mup\) system. Findings suggested protein-protein interactions limited interchangeability of equivalent functions between two biosynthetic systems. It was shown by expressing related genes as groups for complementation in the \(mup\) system that it was possible to confirm specificities of such interactions.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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