Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.550318
Title: Chemical arguments shedding light on the biosynthesis of curious natural products
Author: Marshall, James William
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2010
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Abstract:
The study of biosynthesis is fascinating and with progression in molecular biology, understanding of the field is advancing rapidly. Underpinning all areas of biosynthetic research however, is natural product chemistry. The isolation and characterisation of compounds provides the answers to the questions posed by molecular biology and genetics. Isotopic labelling studies also remain fundamental to the identification of biosynthetic pathways, linking compound structures to genes. The biosynthesis of a multipotent stilbene ST 1, produced by a symbiotic bacterium Photorhabdus luminescens, is studied. The results of isotopic labelling experiments are compared to a biosynthesis of ST 1 proposed by other researchers using orthogonal methods. Mutasynthesis experiments are conducted which produce novel analogues of ST 1. A novel natural product, rhabdolactone 2 and its fluorinated un-natural analogue fluororhabdolactone 3, are discovered in P. luminescens cultures during a mutasynthesis experiment. Isotopic labelling is used to study the biosynthesis of rhabdolactone 2 and a biosynthesis is proposed. The biosynthesis of fusarachromene 4, an alkaloid isolated from cultures of Fusarium sacchari, a sugarcane pathogen, is studied using isotopic labelling experiments and an unusual biosynthesis proposed. The enzymology of tenellin 5 biosynthesis is investigated by heterologous gene expression in A. oryzae. Errors in polyketide chain assembly are observed when tenS a gene encoding a PKS-NRPS is expressed in the absence of tenC which encodes an ER. Co-expression of tenS and tenC is required for biosynthesis the correctly constructed polyketide chain. Magnaporthe grisea is a virulent crop pathogen. The virulence of M grisea has been linked to the activity of Acel, a gene which encodes a PKS-NRPS. The hypothetical ACEl compound has not previously been reported. The isolation and characterisation of a novel pyrone 6 believed to be the oxidised product of the ACEl PKS is described following the successful heterologous expression of Ace1 in A. oryzae.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.550318  DOI: Not available
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