Community Research and Development Information Service - CORDIS

FP6

COMBIG-TOP — Result In Brief

Project ID: 503491
Funded under: FP6-LIFESCIHEALTH
Country: Germany

Treating life-threatening hospital infections

Due to widespread use of antibiotics, many bacterial pathogens have become resistant to existing pharmaceuticals. EU-funded researchers developed novel natural production systems for generating better and safer antibiotics from biological molecules.
Treating life-threatening hospital infections
Bacterial resistance to antibiotics is particularly dangerous in light of the increasing frequency of life-threatening infections contracted in hospitals by already compromised patients.

Glycopeptides, molecules that play a critical role in formation of cell walls in bacteria, are excellent candidates for the development of antibiotics. In fact, glycopeptide-based antibiotics have been used in Europe and to a lesser extent in the United States, primarily to treat such life-threatening situations as potential adverse side-effects have prohibited more widespread use.

However, glycopeptides are complex biological molecules whose twisted three-dimensional (3D) structure has made it difficult to make specific modifications for better drug development.

European researchers initiated the ‘Combinatorial biosynthesis of industrial glycopeptides: Technology, optimization and production’ (Combig-TOP) project to develop new glycopeptide drug candidates as well as effective tools for bringing drugs to market quickly.

They employed a technique called combinatorial biosynthesis that enabled them to access the core of the glycopeptide molecule and design more effective analogues via site-specific chemical modifications.

In addition, this methodology was used to replace time-consuming chemical synthesis with rapid fermentation based on identification of an ideal host organism for glycopeptide production. In fact, using acquired knowledge of the biosynthetic pathway, scientists were able to produce mutations and protocols leading to useful overproduction of glycopeptides.

Two research-based small and medium-sized enterprises (SMEs) participated in the project to quickly bring results to market.

Overall, the Combig-TOP project successfully manipulated two glycopeptide producer strains and established both the feasibility and the limitations of novel glycopeptide synthesis for development of more effective antibiotics.

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