Objectif 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. Champ scientifique 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 Mots‑clés 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. Thème(s) LSH-2002-1.2.5-3 - Combinatorial biosynthesis as a tool for generating new drug candidates Appel à propositions FP6-2002-LIFESCIHEALTH Voir d’autres projets de cet appel Régime de financement STREP - Specific Targeted Research Project Coordinateur EBERHARD KARLS UNIVERSITAET TUEBINGEN Contribution de l’UE Aucune donnée Adresse Wilhelmstrasse 7 TUEBINGEN Allemagne Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée Participants (8) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire RIJKSUNIVERSITEIT GRONINGEN Pays-Bas Contribution de l’UE Aucune donnée Adresse Broerstraat 5 PO BOX 72 GRONINGEN Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée FLUXOME SCIENCES Danemark Contribution de l’UE Aucune donnée Adresse Soltofts Plads, Building 223 LYNGBY Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée PILIPPS UNIVERSITAT MARBURG Allemagne Contribution de l’UE Aucune donnée Adresse Biegenstra?e 10 MARBURG Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée TECHNICAL UNIVERSITY OF DENMARK Danemark Contribution de l’UE Aucune donnée Adresse Anker Engelundsvej 1 KGS. LYNGBY Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée COMBINATURE BIOPHARM AG Allemagne Contribution de l’UE Aucune donnée Adresse Robert-Rossle-Str. 10 BERLIN Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée UNIVERSITA DI PALERMO - DIPARTIMENTO DI BIOLOGIA CELLULARE E DELLO SVILUPPO Italie Contribution de l’UE Aucune donnée Adresse Viale delle Scienze - Parco d'Orleans II' PALERMO Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée UNIVERSITY OF ZURICH Suisse Contribution de l’UE Aucune donnée Adresse Raemistrasse 71 ZURICH Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée TECHNISCHE UNIVERSITAT BERLIN Allemagne Contribution de l’UE Aucune donnée Adresse Stra?e des 17. Juni 136 BERLIN Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée