Award details

Expression of novel actinobacterial TypeIII polyketide synthase (PKS) genes: towards new natural product discovery

Reference	BBS/E/J/000CY040
Principal Investigator / Supervisor	Professor Mervyn Bibb
Co-Investigators / Co-Supervisors
Institution	John Innes Centre
Department	John Innes Centre Department
Funding type	Research
Value (£)	3,106
Status	Completed
Type	Institute Project
Start date	01/07/2008
End date	30/06/2010
Duration	24 months

Abstract

Type III polyketides are relatively little studied compounds mainly produced by plants but recently found to be made by certain soil dwelling bacteria known as actinomycetes). Bacterial Type III polyketides are made by Type III polyketide synthases (PKS) that are responsible for sequential addition of CoA-linked acetate derived substrates. Structural diversity within this family of molecules results from the selection of different starter substrates, from differing numbers of condensation reactions (i.e. extender units), and from the pattern of final ring closure. Type III polyketides are thus attracting significant attention because of their novel structures and their potential to yield valuable pharmaceutical products. While bacterial genome sequencing is yielding increasing numbers of bacterial Type III PKSs, only a few have been characterised biochemically. In this project, we plan to isolate Type III PKS genes from culturable rare actinomycetes, a proven source of novel chemical diversity (these organisms produce the vast majority of antibiotics used in medicine) and from non-culturable actinomycetes which represent a thus far untapped source of structural diversity. The objectives of the project are as follows. 1. Using PCR methodology to identify novel Type III PKS genes from a collection of rare actinomycetes and from metagenomic DNA libraries. The genes will be characterised by phylogenetic analysis. 2. Expression of novel Type II PKS genes in Escherichia coli and Streptomyces lividans. 3. Characterisation of the Type III polyketides produced using appropriate physical and chemistry techniques (HPLC and high accuracy mass spectrometry). The methods developed in the project will allow the exploration and exploitation of novel Type III polyketides. The diversity of Type III polyketide compounds produced using this approach will provide an excellent opportunity to further evaluate the pharmaceutical value of these relatively uncharacterised family of compounds.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Industrial Biotechnology, Microbiology
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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