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Content archived on 2024-05-29

A modular platform for biosynthesis of complex molecules

Objective

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 s tructures 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 netw ork 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 c omplex saccharide structures for which no economic synthesis scheme exists to date. We will use a forward engineering approach in order a) to modularise Escherichia coli's cell metabolism into an energy module and a synthetic module for saccharide p roduction and b) 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 esse ntially 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" (SBT) will be used for saccharide produc tion 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 targe t the facile and inexpensive design of inaccessible oligosaccharides.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Call for proposal

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FP6-2003-NEST-PATH
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Funding Scheme

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STREP - Specific Targeted Research Project

Coordinator

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
EU contribution
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Total cost

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Participants (3)

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