EUROBIOSYN: A modular platform for biosynthesis of complex molecules
Duration: 36 months
Coordinator: Swiss Federal Institute of Technology Zurich (Switzerland)
Contact Person:Prof. Sven Panke Swiss Federal Institute of Technology Zurich Sonneggstrasse 5 8092 Zurich, Switzerland e-mail: panke[at]ipe.mavt.ethz.ch tel:+41 44 632 04 13 fax: +41 44 632 13 25
- Stuttgart University (Germany)
- Technical University of Denmark (Denmark)
- National Biotechnology Centre (Spain)
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 subcellular proportion that mimics cell metabolisms 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 1. to modularise Escherichia coli’s cell metabolism into an energy module and a synthetic module for saccharide production and 2. to adapt the modules’ productivity by reengineering its key enzymes However, such a cell modularisation is incompatible with cell viability, which is 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” (SOB) 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 simple design of inaccessible oligosaccharides.