FP6 - 12749 (NEST) EUROBIOSYN - A molecular platform for biosynthesis of complex molecules

Contacts
Website: www.eurobiosyn.org




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Biological Conversion : Biotechnology : NEST - New and Emerging Science and Technology

Type of Project	NEST
Contract No	FP6 - 12749
Total Cost	2,742 KEuro
EC Contribution	1,260 KEuro
Start Date	1-1-2005
Duration	36 Months

Abstract

Economic synthesis of mono- and oligosaccharides represents a pressing, formidable and essentially unresolved challenge of strategic importance against the background of the emerging field of glycomics and the increasing importance of (oligo)saccharide structures in modern therapeutics.

Enzyme-based methods are considered particularly promising here because of their unmatched selectivity. However, designing a scheme from monosaccharide to oligosaccharide synthesis will require an enzymatic reaction network of sub-cellular proportion that mimics cell metabolism's complexity, dynamic behaviour and energy requirements.

Utilising a synthetic biology approach, EUROBIOSYN targets the construction of a modular platform for the highly efficient synthesis of complex saccharide structures for which no economic synthesis scheme exists to date. We will use a forward engineering approach in order

• to modularise Escherichia coli's cell metabolism into an energy module and a synthetic module for saccharide production and
• to adapt the modules' productivity by reengineering its key enzymes

However, such a cell modularisation is incompatible with cell viability, which explains why we will follow a novel three-phase approach: after a growth phase of an essentially wild-type E. coli cell, the flipping of a switch will induce the second phase's modularisation through a major reorganisation of the cellular proteome, and only the resulting "system of biotransformations" will be used for saccharide production in the third phase.

We will demonstrate the feasibility of the concept with the one-pot, one-step production of dihydroxyacetone phosphate (DHAP)-derived monosaccharides for pharmaceutical applications. By adding more modules in the future, we target the facile and inexpensive design of inaccessible oligosaccharides.

Coordinator

Eidgenoessische Technische Hochschule Zurich, Switzerland

Partners

• Institute of Technical Biochemistry, Bioinformatics, Stuttgart University, Germany
• Department of Chemical Engineering, Technical University of Denmark, Denmark
• Centro Nacional de Biotechnologia, Madrid, Spain

Contacts

Contact

• Eidgenoessische Technische Hochschule Zurich Institute of Process Engineering / SWITZERLAND