FP6 - 503491 COMBIG-TOP: Combinatorial Biosynthesis of Industrial Glycopeptides: Technology, Optimization and Production

Contacts




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Biotechnology : Chemical Conversion : Crops for Pharmaceuticals/Cosmetics : Life Science and Food Quality

Type of Project	STREP
Contract No	FP6 - 503491
Total Cost	2,600 KEuro
EC Contribution	2,000 KEuro
Start Date	29-12-2004
Duration	Months

Abstract

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.

Coordinator

Eberhard Karls-Universität Tübingen, Germany

Partners

• Danmarks Tekniske Universitet, Denmark
• Vicuron Pharmaceuticals, Italy
• Combinature Biopharm Ag, Germany
• Philipps University Marburg, Germany
• Universita Degli Studi Di Palermo, Italy
• Universitaet Zuerich, Switzerland
• Rijksuniversiteit Groningen, Netherlands

Contacts

Contact

• Wolfgang WOHLLEBEN / Eberhard Karls-Universität Tübingen Department of Microbiology/Biotechnology / GERMANY