Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/8720
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Harrison, P. | en_US |
dc.contributor.author | Saepudin, Endang | en_US |
dc.date.accessioned | 2014-06-18T16:43:47Z | - |
dc.date.available | 2014-06-18T16:43:47Z | - |
dc.date.created | 2011-02-10 | en_US |
dc.date.issued | 1995-05 | en_US |
dc.identifier.other | opendissertations/3901 | en_US |
dc.identifier.other | 4918 | en_US |
dc.identifier.other | 1775907 | en_US |
dc.identifier.uri | http://hdl.handle.net/11375/8720 | - |
dc.description.abstract | <p>The naturally occurring antibiotic β-lactone F-244, also known as 1233A and L-659,699, is isolated from species of Fusarium, Scopulariopsis and Cephalosporium. This compound has been shown to be a potent specific inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase, a key enzyme in the mammalian biosynthesis of cholesterol.</p> <p>Extensive multidimensional NMR analysis afforded unambiguous assignments of all the proton and carbon-13 resonances of F-244.</p> <p>The biosynthesis of F-244 in Fusarium sp. ATCC 20788 was investigated by incorporation of isotopically labelled precursors such as acetate and methionine into growing cultures. Separation and purification of the resulting labelled F-244 was followed by NMR analysis to determine the location of label.</p> <p>The results show that F-244 is a polyketide metabolite derived from 7 acetate units arranged in a typical "head-to-tail" fashion; the three methyl groups and the carbon of the hydroxymethyl moiety are derived from L-methionine. The carbonoxygen bonds at C₁₄=O and C₁₂-O are derived intact from acetate. These results define a probable sequence of events on the polyketide synthase surface, where acetate units are condensed and manipulated to give F-244.</p> <p>To test this hypothesis, several of the potential intermediates, both as free acids and as N-acetylcysteamine thioesters, with strategically placed deuterium or carbon-13 labels, were synthesized and fed to growing cultures of Fusarium sp. ATCC 20788.</p> <p>The results of feeding experiments using deuterium labelled putative intennediates showed that none of these precursors was incorporated intact. When the carbon-13 labelled intermediates were used, the ¹³C NMR spectra showed enhancements of the signals that are derived from C-1 of acetate, indicating that the labelled intermediates had been degraded by β-oxidation.</p> <p>[equations removed]</p> | en_US |
dc.subject | Chemistry | en_US |
dc.subject | Chemistry | en_US |
dc.title | The Biosynthesis of Antibiotic F-244 in Fusarium sp. Atcc 20788 | en_US |
dc.type | thesis | en_US |
dc.contributor.department | Chemistry | en_US |
dc.description.degree | Doctor of Philosophy (PhD) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Size | Format | |
---|---|---|---|
fulltext.pdf | 6.13 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.