Award details

The pyrrolnitrin biosynthetic pathway

Reference	BB/C000080/1
Principal Investigator / Supervisor	Professor James Naismith
Co-Investigators / Co-Supervisors
Institution	University of St Andrews
Department	Chemistry
Funding type	Research
Value (£)	369,611
Status	Completed
Type	Research Grant
Start date	02/05/2005
End date	01/05/2010
Duration	60 months

Abstract

This is a five year proposal to study three entirely novel enzyme activities, chlorination, ring re-arrangement and amine oxidation. This will be done by studying a pathway of four enzymes (PrnA, PrnB, PrnC and PrnD), two of which (PrnA and PrnC) are chlorinases. The pathway makes pyrrolnitrin, a potent antifungacide which contains two chlorine atoms starting from tryptophan. The addition of chlorine is central to many biosynthetic pathways including vancomycin. The mechanism of this transformation is urgently sought and several hypotheses have been made. A detailed understanding of the mechanism including its substrate specificity will help in a manufacture of new biologically active compounds by fermentation. The other two activities are fascinating from a biochemical standpoint and may help interpret secondary metabolism in other organisms. Both are predicted to have novel enzyme mechanisms. The study of novel enzymes can lead to insight into designing new strategies or reagents for organic synthesis. Modification of these enzymes can yield catalysts useful in organic synthesis. An aim of the work is to see whether the substrate profile can be extended. The following preliminary data has been supplied structure of PrnA (the first structure of a bacterial non-metal centred halogenase). We have expressed all the target enzymes, identified orthologues, assays and synthesis of substrates.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	Industrial Biotechnology, Microbiology, Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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