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Project 10:

Global metabolic switching in Streptomyces coelicolor


Antibiotics are made during the second phase of growth when there is a transition in metabolism from primary to secondary metabolism. Primary metabolism is growth related and involves all the normal cellular activities associated with cell growth and division. Whereas secondary metabolism is non-growth linked and is non-essential but many important activities occur during this phase which help the bacterium survive.


One of these activities is antibiotic production and is widespread in streptomycetes found in most soils. These bacteria have a fascinating life history and are abundant producers of biologically active compounds many of which have been exploited for their anti-tumour, anti-bacteria and anti-fungal activity.


Our research will improve our understanding of how these bacteria regulate the transitions from primary to secondary metabolism and provide mathematical models to simulate the metabolic switch of life styles.



Source: E.M.H. Wellington
 
Source: E.M.H. Wellington

The approach is regarded as a ?systems? analysis where a model is built of the whole metabolism and it can predict outcomes that will not have been determined previously by experimental methods. A range of modelling tools will be provided and these will be available for use with many other projects involved in a systems approach. The fuller understanding of the metabolic switch and the elucidation of how and why certain antibiotics are made under defined growth conditions will be vital for the exploitation of these bacteria. Many tools are available to manipulate bacterial genomes and with an understanding of the metabolism it will be possible to manipulate growth in order to produce novel antibiotics.



Project Partners: (click web links for detailed information)


Elizabeth M. H Wellington, University of Warwick, UK (Project Coordinator)
David A. Rand, University of Warwick, UK
Nigel J. Burroughs, University of Warwick, UK
David A. Hodgson, University of Warwick, UK
Gregory L. Challis, University of Warwick, UK
Margeret C. M. Smith, University of Aberdeen, UK
Preben Krabben, University of London UCL, UK
Wolfgang Wohlleben, University of Tuebingen, Germany
Kay Nieselt, University of Tuebingen, Germany
Lubbert Dijkhuizen, University of Groningen, The Netherlands [MicPhys] [GBB]
Rainer Breitling, University of Groningen, The Netherlands [GBiC] [GBB]
Eriko Takano , University of Groningen, The Netherlands [MicPhys] [GBB]
Juan-Francisco Martín, INBIOTEC Leon, Spain
Trond E. Ellingsen, SINTEF, Norway
David L. Wild, University of Warwick, UK