Award details

Structure function and protein engineering of antibiotic-producing polyketide synthases

Reference	SF11231
Principal Investigator / Supervisor	Professor Peter Leadlay
Co-Investigators / Co-Supervisors
Institution	University of Cambridge
Department	Biochemistry
Funding type	Research
Value (£)	439,336
Status	Completed
Type	Fellowships
Start date	01/01/1999
End date	01/01/2004
Duration	60 months

Abstract

This project is chiefly aimed at obtaining high resolution structural information for the modular polyketide synthases (PKSs). Since the modular polyketide synthases are among the largest multienzymes known (molecular mass of the erythromycin PKS is 2Mda, of the rapamycin PKS is 5.6MDa, and estimated molecular mass of the amphotericin PKS is 8-10MDa) there is a significant technical challenge involved. However the modular nature of these enzymes means that it is possible to define smaller structural units whose X-ray crystal structure would reveal a wealth of information about the overall architecture of these enzymes. Natural polyketides include a number of outstandingly valuable drugs, and it is possible that the structural information will be of real assistance in the engineering of PKS enzymes to produce new medicines or more effective versions of existing ones, and thereby to benefit the quality of life. The platform for this project is an existing interdisciplinary research programme at the University of Cambridge involving both chemists and biologists, which has been increasingly fostered over the last eight years by the Research Councils, with additional support from medical research charities and from industry. The objectives of the proposed research programme are: a) Determination of the X-ray crystal structure of (at least key portions of) a modular antibiotic-producing polyketide synthase (PKS) (in collaboration with Professor Sir Tom Blundell/ Dr Nick Keep. b) Investigation of protein-protein interactions in a modular antibiotic- producing PKS.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Fellowship - Professorial Fellowship (PF) [1996-2009]
Funding Scheme	X – not Funded via a specific Funding Scheme

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