Graham Cromar

From

Graham Cromar

Supervisor: John Parkinson, Research Institute of the Hospital for Sick Children, enrolled in Department of Molecular and Medical Genetics

WiP Seminar, 12 May 2009

iGEM 2009 - Building a standard platform to investigate the potential of Enzyme Channeling

Enzyme channeling has the potential to increase the efficiency of some otherwise thermodynamically unfavorable reactions through the co-localization of enzymes catalyzing adjacent steps in a biochemical reaction. In addition, channeling may also be involved in pathway switching, preventing escape of small molecules, preventing accumulation of toxic intermediates and preventing the breakdown of unstable intermediates. In nature, this is accomplished by a number of mechanisms including protein fusion together with further surface charge adaptations which optimize delivery of reaction intermediates from one active site to another, trafficking of enzymes to the same cellular compartment, the use of complexes and membrane scaffolds. Recently, Chris Sanford in our laboratory has explored the effect of channeling using a three dimensional lattice simulation environment (Cell++) which has been uniquely designed to consider the spatial relationships of component objects when simulating cell processes. This is particularly important because the role of spatial organization in biological pathways has typically been neglected in simulations. The results suggest that the simple colocalization of enzyme pairs with certain properties can affect the rates of accumulation of reaction intermediates in a pathway. Under the auspices of the international genetically engineered machine (iGEM) competition, a team of undergraduates will test this prediction using a synthetic biology approach to construct a standard, re-usable platform capable of co-localizing chosen enzyme pairs. We will use this platform to investigate channeling in predicted enzyme pairs with an emphasis on pathways that may be of biological or commercial interest. See www.igemtoronto.org.

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