Objective "Secondary metabolites (SMs) of bacterial origin play a pivotal role in modern therapy of various diseases. Whole-genome sequencing projects have revealed that all SM producing organisms have the capacity to produce many more compounds than reported from the respective strains. Despite their importance and their broad use in medicine, we hardly know anything about (i) the natural function of these important compounds, (ii) the underlying regulatory networks, and (iii) how to increase the number and yield of SMs produced by a single organism.PROSECMET will address all these issues through the activities in four different work packages. As model organisms Photorhabdus and Xenorhabdus bacteria will be used that live in symbiosis with nematodes and together with them form an entomopathogenic complex.WP1-Identification of SM targets. Derivatives of SMs will be synthesized allowing the identification of their molecular targets in bacteria, nematodes, insects and/or food competitors using methods of chemical biology.WP2-Regulatory networks. External factors that activate SM production and if and how SMs act as internal signals in the producer will be identified (eg. by flow cytometry) with specific strains carrying SM biosynthesis gene promoters or promoter libraries fused to genes encoding different reporters (fluorescent proteins, resistance genes).WP3-Increasing chemical diversity. Factors identified in WP2 will be applied to at least 100 different Photorhabdus and Xenorhabdus isolates in order to increase the number and the yield of SMs produced by them. Additionally, the genome of selected isolates will be sequenced in order to exchange the promoters responsible for SM biosynthesis leading to the production of additional compoundsWP4-Optimization of SM production. Using either regulatory elements identified in WP2 or artificially designed regulators, cell growth will be coupled to SM production, thus enabling the systematic construction of SM overproducers." Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesbiological behavioural sciencesethologybiological interactionsnatural sciencesbiological scienceszoologyentomologynatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS9 - ERC Starting Grant - Applied life sciences and biotechnology Call for proposal ERC-2012-StG_20111109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN Address Theodor w adorno platz 1 60323 Frankfurt am main Germany See on map Region Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Kristina Wege (Ms.) Principal investigator Helge Björn Bode (Prof.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN Germany EU contribution € 1 754 700,00 Address Theodor w adorno platz 1 60323 Frankfurt am main See on map Region Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Administrative Contact Kristina Wege (Ms.) Principal investigator Helge Björn Bode (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
