| EPSRC Reference: |
GR/N63529/01 |
| Title: |
BIOSYNTHETIC STUDIES ON AZIRIDINE-CONTAINING NATURAL PRODUCTS - THE AZINOMYCINS AND FICELLOMYCIN |
| Principal Investigator: |
Lowden, Dr PAS |
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| Project Partners: |
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| Department: |
Chemistry |
| Organisation: |
University of Exeter |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 October 2000 |
Ends: |
30 September 2003 |
Value (£): |
62,587
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| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
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| EPSRC Industrial Sector Classifications: |
| Pharmaceuticals and Biotechnology |
No relevance to Underpinning Sectors |
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Summary on Grant Application Form |
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The azinomycins are anticancer compounds that contain the highly stranded 1-azabicyclo(3.1.0)hexane ring system, which plays an important role in their biological activity. Ficellomycin is an antibiotic which also contains this unusual structural feature. A detailed understanding of the biosynthesis of these compounds would allow the biosynthetic engineering of analogues with potentially improved biological activity. The principal aim of this project is to define the biosynthetic pathway to these compounds as an essential prelude to more detailed studies of the genetics and enzymology of this pathway.13C-labelled primary metabolic precursors such as glucose and pyruvate will be fed to establish the origin of the carbon atoms in the azinomycins and ficellomycin. More advanced intermediates on the proposed pathway will be synthesised stereospecifically in 2H- and 13C-labelled form and fed to the produced organisms. Incorporation patterns will be analysed by mass spectrometry and 2H- or 13C-NMR.If time allows, analogues of proposed biosynthetic intermediates will be fed to investigate the substrate flexibility of the biosynthetic enzymes, and any new compounds produced in this way will be tested for biological activity. In addition, studies will be initiated to isolate and characterise the biosynthetic enzymes.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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| Date Materialised |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.ex.ac.uk |