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Title: Molecular probes for the evaluation of three isomerase enzyme mechanisms in secondary metabolism
Author: Nasomjai, Pitak
ISNI:       0000 0004 2719 1716
Awarding Body: University of St Andrews
Current Institution: University of St Andrews
Date of Award: 2010
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This thesis is focused on an investigation of the mechanisms of three enzymatically mediated carbon skeleton isomerisation reactions. Chapter 1 provides an overview of some representative examples of the carbon skeleton rearrangement reactions in enzymology. Chapter 2 describes the preparation and use of fluorolittorines to explore the mechanism of the rearrangement of the tropane alkaloid littorine to hyoscyamine which is a reaction mediated by the cytochrome P450 enzyme. Chapter 3 describes the synthesis of D-ribose-1-phosphonates and the cyclic phosphonates (phostone) that are candidate inhibitors of the enzymatic isomerisation of 5-fluoro-5-deoxy-ribose-1-phosphate (5-FDRP) to 5-fluoro-5-deoxy-ribulose-1-phosphate (5-FDRulP), an important step in fluorometabolite biosynthesis pathway in Streptomyces cattleya. Chapter 4 describes the synthesis of 5-hydroxy-3,4-dioxohexylphosphonate and [5-13C]-5-hydroxy-3,4-dioxohexylphosphonate. These compounds are proposed as candidates for the transition state of the retro-aldol/aldol mechanism of the enzymatic isomerisation of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methylerythitol-phophate-2-phosphate (MEP) in the biosynthesis of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). The influence of pH on tautomerisation of [5-13C]-5-hydroxy-3,4-dioxohexylphosphonate is also described. Chapter 5 describes the general chemical and biochemical methodologies utilised in this research project.
Supervisor: O'Hagan, David Sponsor: Royal Thai Government
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Isomerisation ; Alkaloid ; Cytochrome P450 ; Fluorometabolite ; 5-fluoro-5-deoxyribulose-1-phosphate ; Phostone ; 2-C-methylerythitol-phophate-2-phosphate ; QD281.R35N2 ; Isomerization ; Enzymology ; Metabolism ; Secondary