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Delta 56-desaturation of sterols: defining the enzymology and role in azole antifungal resistance

Reference	P11059
Principal Investigator / Supervisor	Professor Steven Kelly
Co-Investigators / Co-Supervisors	Professor David Lamb
Institution	Aberystwyth University
Department	Inst of Biological, Environ & Rural Sci
Funding type	Research
Value (£)	189,030
Status	Completed
Type	Research Grant
Start date	01/01/2000
End date	01/01/2003
Duration	36 months

Abstract

Sterol delta 5,6 desaturase is a late step in sterol biosynthesis that is important for osmotic robustness of membranes e.g. against ethanol. It is our hypothesis that this enzyme is central to the mode of action of azole antifungals against Candida in the clinic. The investigation of the enzyme system supporting sterol delta 5,6 desaturation in yeast will be undertaken using genome information, purified enzymes and substrates in the first example of detailed biological chemistry on this system. The molecular basis of mutations conferring stringent and leaky blocks in the yeast gene ERG3 encoding the desaturase (an oxygenase) will be examined and structure/function studies developed through site-directed mutagenesis of the putative iron-binding motif. The same gene in clinical azole resistant Candida strains is defective and the molecular events occurring in this practical setting will be revealed.

Summary

unavailable

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	X – not assigned to a current Research Topic
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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