Objective The focus of this proposal is on glycopeptides, a class of antibiotics where room for improvement is anticipated and the second-generation glycopeptide dalbavancin is under development by one SME of this team. The objectives of this proposal are directed at generating more effective glycopeptides by combinatorial biosynthesis and at speeding up the development of promising glycopeptides through improvement of the fermentation process. The project will start with the generation of novel peptide backbones, either chemically or by exchanging gene fragments determining amino acid specificity. Genes involved in subsequent tailoring reactions, such as the coupling reactions, glycosyl transfer, halogenation, and the supply of activated sugars or amino acid precursors will be collected from glycopeptide producers or identified by genetic screening. Knowledge of the enzymatic reactions will enable gene combinations to generate novel glycopeptides with altered backbones, novel glycosylation patterns, and other modifications. These compounds will be tested for their effectiveness as antibiotics. To bring forward drug candidates, we will combine post-genomics techniques (proteome/transcriptome) with modern molecular biotechnology to optimise the production process. This will be achieved by flux analyses and 2D-maps for discovering primary metabolism proteins up-regulated during glycopeptide production. Combined with a study of other limiting steps, such as precursor uptake and productexcretion, and with transcriptional regulation of glycopeptide genes, bottlenecks in production will be identified and eliminated, allowing the construction of an improved production strain, usable also for the novel glycopeptides generated by the project. By combining combinatorial biosynthesis integrated with modern molecular techniques, high quality academic research becomes tightly interconnected with industrial research and production processes. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinepharmacology and pharmacypharmacokineticsmedical and health sciencesbasic medicinephysiologynatural scienceschemical sciencesorganic chemistryamines Keywords antibiotics infection resistance Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) LSH-2002-1.2.5-3 - Combinatorial biosynthesis as a tool for generating new drug candidates Call for proposal FP6-2002-LIFESCIHEALTH See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator EBERHARD KARLS UNIVERSITAET TUEBINGEN EU contribution No data Address Wilhelmstrasse 7 TUEBINGEN Germany See on map Links Website Opens in new window Total cost No data Participants (8) Sort alphabetically Sort by EU Contribution Expand all Collapse all RIJKSUNIVERSITEIT GRONINGEN Netherlands EU contribution No data Address Broerstraat 5 PO BOX 72 GRONINGEN See on map Links Website Opens in new window Total cost No data FLUXOME SCIENCES Denmark EU contribution No data Address Soltofts Plads, Building 223 LYNGBY See on map Links Website Opens in new window Total cost No data PILIPPS UNIVERSITAT MARBURG Germany EU contribution No data Address Biegenstra?e 10 MARBURG See on map Links Website Opens in new window Total cost No data TECHNICAL UNIVERSITY OF DENMARK Denmark EU contribution No data Address Anker Engelundsvej 1 KGS. LYNGBY See on map Links Website Opens in new window Total cost No data COMBINATURE BIOPHARM AG Germany EU contribution No data Address Robert-Rossle-Str. 10 BERLIN See on map Links Website Opens in new window Total cost No data UNIVERSITA DI PALERMO - DIPARTIMENTO DI BIOLOGIA CELLULARE E DELLO SVILUPPO Italy EU contribution No data Address Viale delle Scienze - Parco d'Orleans II' PALERMO See on map Links Website Opens in new window Total cost No data UNIVERSITY OF ZURICH Switzerland EU contribution No data Address Raemistrasse 71 ZURICH See on map Links Website Opens in new window Total cost No data TECHNISCHE UNIVERSITAT BERLIN Germany EU contribution No data Address Stra?e des 17. Juni 136 BERLIN See on map Links Website Opens in new window Total cost No data