A combined theoretical and experimental approach to the study of metabolic channeling

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Cellular metabolism represents a collection of enzymatic reactions and transport processes that convert metabolites into the molecules required for life. Typically enzymes operate as a collective system within the context of functional pathways. Recent studies have revealed that these pathways exhibit a high degree of spatial organization either through the formation of sub-cellular compartments or protein complexes. Such organization provides a mechanism to 'channel' a substrate from one enzyme to another, increasing product yield and reaction efficiency. Through spatially coordinating enzymes within pathways, there is an opportunity to translate the potential benefits of channeling to many applications currently being targeted by metabolic engineering. In a novel and multi-disciplinary approach combining bioinformatics with computer simulations, we propose to systematically identify the conditions required for channeling to operate and improve pathway performance. By predicting reactions which are most likely to benefit from channeling, this knowledge will be exploited to design synthetic pathways more effectively.