MEMORE: Metabolic Engineering and Dynamic Modelling of E. coli for the Production of Chemicals from Renewable Resources

This research project aims to develop and provide the tools and know-how to speed up and improve the development process

Industrial biotechnology uses biological systems for the production of useful chemical substances. One of the key technologies for industrial biotechnology is metabolic engineering. By this technique, micro-organisms can be improved to produce metabolites with a better yield. By extending their metabolism with novel synthetic pathways, they can even be programmed to produce new metabolites that these organisms do not naturally synthesize. The presently used approach in metabolic pathway engineering of micro-organisms is to make an educated guess based on biochemical knowledge of synthesis pathways about which modification might improve or redirect the metabolic flux to a particular compound. This principle must then be put in practice by genetically modifying the micro-organism, after which the assumption can be checked experimentally. This can only be done after the time- and money-consuming process of genetic modification of the production strain. Furthermore, it is fairly typical to obtain surprises: the complicated cellular network of metabolic fluxes and its regulation mechanisms is indeed designed to prevent overproduction, leading to unexpected and counter-intuitive findings in practice. Consequently, a fair number of modifications are required to obtain a good result, typically obtained the hard way by a long trial and error process. This research project aims to develop and provide the tools and know-how to significantly speed up and improve this development process. It aims to develop a methodology to build dynamic mathematical models of the central metabolism of micro-organisms in which all major metabolic fluxes are considered. The speed of obtaining results from the model simulation ("in silico experiments") must permit to better define the targets for metabolic pathway engineering, before actually performing experimentally the tedious genetic engineering work necessary to obtain such modified micro-organism. E. coli will be used as a model organism to develop the general methodology and gain expertise. By using this dynamic metabolic model, the envisaged pathway modifications or pathway extensions can be simulated "in silico" to predict their effects. The use of this model will also allow for a better understanding of the metabolic flux in micro-organisms and the optimisation of fermentation conditions, particularly of fed-batch fermentations. After having developed the methodology and the metabolic model of the central metabolism of E. coli, this will be put to the test by designing an E. coli strain that overproduces succinate.

Project duration: 2005-03-01 - 2009-02-28

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Dr. ir. Gino JE Baart
Department of Applied Mathematics, Biometrics and Process Control
Coupure Links 653
9000 Gent
Tel: +32 (0)9 264 6196
Fax: +32 (0)9 264 6220

Last update: 01 december 2008,

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