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Details of Grant 

EPSRC Reference: GR/S78124/01
Title: Chemical Analysis of the Mupirocin Gene Cluster from Pseudomonas fluorescens
Principal Investigator: Simpson, Professor TJ
Other Investigators:
Cox, Professor R Willis, Professor C Crosby, Dr J
Thomas, Professor CM
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: University of Bristol
Scheme: Standard Research (Pre-FEC)
Starts: 01 October 2004 Ends: 31 December 2007 Value (£): 335,522
EPSRC Research Topic Classifications:
Biological & Medicinal Chem. Bioprocess Engineering
Chemical Biology
EPSRC Industrial Sector Classifications:
Pharmaceuticals and Biotechnology
Related Grants:
Panel History:  
Summary on Grant Application Form
Mupirocin (pseudomonic acid) is a structurally unusual polyketide antibiotic, which also displays a unique mode of action giving it potential for the treatment of multi-resistant bacteria. Due to its inherent instability in serum its use has been limited and so production of more stable active analogues is desirable. However its structural complexity makes realisation of this goal by traditional medicinal chemistry approaches problematic. Isolation and analysis of it biosynthetic gene cluster reveals a structure quite unlike any previously studied polyketide. Complete analysis of its gene cluster will require extensive chemical-based studies to complement on-going genetic manipulations. Combined chemical and genetic studies to achieve a full understanding of the details of mupirocin biosynthesis in Pseudomonas fluorescens could enable the production of analogues by rational manipulation of the biosynthetic genes to produce predictable alterations of structure. Very recent work has indicated that some other biologically interesting and evolutionary diverse systems may have generic similarities to mupirocin at the genetic level so this work will have wider implications for our ability to produce novel bioactive compounds by the combinatorial biosynthetic approach.
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Organisation Website: http://www.bris.ac.uk