The Bristol Polyketide Group are engaged in multidisciplinary studies on natural product biosynthesis, particularly those produced by the polyketide biosynthetic pathway, in fungi and bacteria. The work involves isolation and structure elucidation of metabolites from wild type organisms and strains with targeted mutations of the biosynthetic gene clusters; isolation and heterologous expression of polyketide biosynthetic genes, epigenetic studies and overexpression and structural and biochemical characterisation of pathway enzymes.
Three topics illustrating aspects of our work will be described.
- Production of new metabolites related to the anti-MRSA antibiotics mupirocin and thiomarinol in the bacteria Pseudomonas fluorescens and Alteromonas rava.1
- Heterologous expression and “domain swaps” in the multi-domain polyketide synthases responsible for the biosynthesis of the fungal pyridones tenellin and bassianin in Beauvaria bassiana which lead to the first understanding of control of “programming” in the assembly of fungal polyketide metabolites.
- Biosynthetic experiments leading to an interesting and novel biosynthetic pathway to the novel mycotoxin-related metabolite, fusarochromene, in Fusarium sacchari.
- Engineered Thiomarinol Antibiotics Active Against MRSA are Generated by Mutagenesis and Mutasynthesis of Pseudoalteromonas SANK73390. A. C. Murphy, D. Fukuda, Z. Song, J. Hothersall, R. J. Cox, C. L. Willis, C. M. Thomas and T. J. Simpson, Angew. Chem. Int. Ed., 2011, 50, 3271-3274.
- Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite. K. M. Fisch, W. Bakeer, A. A. Yakasai, Z. Song, J. Pedrick, Z. Wasil, A. M. Bailey, C. M. Lazarus, T. J. Simpson, and R. J. Cox, J. Am. Chem. Soc., 2011, 133, 16635-16641.
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http://www.bris.ac.uk/chemistry/people/tom-j-simpson/overview.html
Date: Tuesday, 29 May 2012
Time: 11:30 - 12:30
Venue: The Avogadro – Chemistry Building
Contact person:
Prof Robert Vleggaar : 012 – 420 3095
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