Objective Biosynthetic pathways for selected glycopeptides will be analysed and optimized to mobilize the full potential of the actinomycete Cell Factory in the development and production of improved antibiotics. Glycopeptides are structurally complex molecules so their accessibility to chemistry is severely limited, but room for improvement has been demonstrated. In order to have an impact on the health of EU citizens, improved antibiotics need to be discovered and effectively developed. The objectives of this proposal are the development of effective tools for the engineering of bacterial producers of glycopeptides, the discovery of improved glycopeptide antibiotics and the rapid development of promising antibiotics through optimization of the production process. To achieve these objectives, this proposal gathers an inter-disciplinary team of academic and industrial partners, recognized leaders in the application of tools such as combinatorial biochemistry, biotransformation, protein engineering, artificial chromosomes, synthetic chemistry, molecular genetics, metabolic flux analysis, high throughput screening and medical microbiology.Most of the expected objectives and deliverables were achieved. We havea) completed the DNA sequences of three glycopeptide clusters;b) produced glycopeptide intermediates by genetic manipulation of producer strains;c) overexpressed active oxidases and glycosyltransferases;d) developed a gene transfer system for Nonomuraea and A. mediterranei;e) established a defined medium for Nonomuraea growth and mapped metabolic fluxes;f) implemented a HTS program for hybrid glycosyltransferases;g) generated novel glycopeptides by mutasynthesis;h) generated detailed information on parameters affecting A40926 production.Through these achievements, we can now effectively manipulate two glycopeptide producer strains; we have established the feasibility and limitations to produce novel glycopeptides through chemical, enzymatic, biotransformation and genetic approaches; and we have used the information achieved through the project to develop an efficient process for A40926 production. Fields of science engineering and technologyindustrial biotechnologymetabolic engineeringnatural sciencesbiological sciencesmolecular biologymolecular geneticsmedical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsnatural sciencesbiological sciencesmicrobiology Programme(s) FP5-LIFE QUALITY - Specific Programme for research, technological development and demonstration on "Quality of life and management of living resources", 1998-2002 Topic(s) 1.1.1.-3. - Key action The "Cell factory" Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator BIOSEARCH ITALIA SPA. EU contribution No data Address via Regina Giovanna 17 20129 MILANO Italy See on map Total cost No data Participants (5) Sort alphabetically Sort by EU Contribution Expand all Collapse all TECHNICAL UNIVERSITY OF DENMARK Denmark EU contribution No data Address DTU, blgd. 221 2800 LYNGBY See on map Total cost No data THE UNIVERSITY OF TUEBINGEN Germany EU contribution No data Address Wilhelmstrasse 5 72074 TUEBINGEN See on map Total cost No data UNIVERSITA DEGLI STUDI DI PALERMO Italy EU contribution No data Address PIAZZA MARINA, 61 90133 PALERMO See on map Total cost No data UNIVERSITY OF GRONINGEN Netherlands EU contribution No data Address 4,Nijenborgh 4 9747 AG GRONINGEN See on map Total cost No data UNIVERSITY OF ZURICH Switzerland EU contribution No data Address 71,Raemistrasse 71 CH-8091 ZURICH See on map Total cost No data
