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Metabolic engineering and dynamic modelling of E. coli for the production of chemicals from renewable resources

Joeri Beauprez, Jo Maertens, Maria Foulquié Moreno, Hilal Taymaz, Ellen Van Horen, Gaspard Lequeux, Evelien Vancoppenolle, Raymond Cunin, Mlawule R. Mashego, Aditya Bhagwat, Brecht Donckels, Sarah Boogmans, Dirk De Pauw, Walter van Gulik, Peter A. Vanrolleghem, Sef Heijnen, Dominique Delmeire, Bernard De Baets, Wim Soetaert, Erick Vandamme

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Abstract

Industrial biotechnology uses biological systems for the production of useful chemical substances. This technology has developed into a main contributor to the so-called green or sustainable chemistry, in which renewable resources such as sugars or vegetable oils are converted by micro-organisms into a wide variety of 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. In light of these trends the MEMORE project was founded, to create novel insights in industrial biotechnology and more specifically in the field of metabolic engineering. This project is a multidisciplinary project involving 4 laboratories from Belgium and The Netherlands. About 20 researchers with expertise spanning from genetics over microbial physiology to metabolic modelling and analytics collaborate in this project to develop a dynamic metabolic model of the central metabolism of micro-organisms. With this approach it aims to replace the more commonly used ‘trial and error’ approach for optimization of industrial production processes with the more rational metabolic modelling approach. The constructed dynamic metabolic model simulates “in-silico” envisaged pathway modifications or pathway extensions and predicts its effects. The use of this model allows also 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.

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What this paper is about

Industrial biotechnology uses biological systems for the production of useful chemical substances. This technology has developed into a main contributor to the so-called green or sustainable chemistry, in which renewable resources such as sugars or vegetable oils are converted by micro-organisms into a wide variety of 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. In light of these trends the MEMORE project was founded, to create novel insights in industrial biotechnology and more specifically in the field of metabolic engineering. This project is a multidisciplinary project involving 4 laboratories from Belgium and The Netherlands. About 20 researchers with expertise spanning from genetics over microbial physiology to metabolic modelling and analytics collaborate in this project to develop a dynamic metabolic model of the central metabolism of micro-organisms. With this approach it aims to replace the more commonly used ‘trial and error’ approach for optimization of industrial production processes with the more rational metabolic modelling approach. The constructed dynamic metabolic model simulates “in-silico” envisaged pathway modifications or pathway extensions and predicts its effects. The use of this model allows also 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.

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Available abstract

Industrial biotechnology uses biological systems for the production of useful chemical substances. This technology has developed into a main contributor to the so-called green or sustainable chemistry, in which renewable resources such as sugars or vegetable oils are converted by micro-organisms into a wide variety of 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. In light of these trends the MEMORE project was founded, to create novel insights in industrial biotechnology and more specifically in the field of metabolic engineering. This project is a multidisciplinary project involving 4 laboratories from Belgium and The Netherlands. About 20 researchers with expertise spanning from genetics over microbial physiology to metabolic modelling and analytics collaborate in this project to develop a dynamic metabolic model of the central metabolism of micro-organisms. With this approach it aims to replace the more commonly used ‘trial and error’ approach for optimization of industrial production processes with the more rational metabolic modelling approach. The constructed dynamic metabolic model simulates “in-silico” envisaged pathway modifications or pathway extensions and predicts its effects. The use of this model allows also 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.

Key concepts: Metabolic engineering, Biochemical engineering, Metabolic flux analysis, Biotechnology, Metabolic pathway, Synthetic biology, Biorefinery, Industrial microbiology

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