Systems Biology of a genetically engineered Pseudomonas fluorescens with inducible exopolysaccharide production: analysis of the dynamics and robustness of metabolic networks
“This SysMO sponsored research project systematically explores the dynamics and robustness
of metabolic networks in genetically engineered P. fluorescens bacteria.”
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Overview
This project applies a system biology approach to study the biosynthesis of the industrially important and medically relevant exopolysaccharide alginate network in genetically engineered strains of
Pseudomonas fluorescens. Externally added inducers are used to control alginate production and simulate different levels of the exopolysaccharide alginate network. Network responses from various levels of induction are studied by 'omics techniques in cells growing in continuous cultures, both at steady-state and kinetically as a function of time after induction. Results from the 'omics data analysis are used to construct an
in silico model of the metabolic network involved in alginate production in
Pseudomonas fluorescens. The
in silico model will be used for simulations and refined through further studies of new targeted strain constructions. The project is divided into 4 well defined and highly interconnected
work packages carried out by research institutions in four different European countries: Norway, United Kingdom, Germany and Sweden.
Goals
- Develop an improved in silico genome-scale metabolic model for analysis of metabolism in Pseudomonas fluorescens. The model will be used as a simulation tool to understand and predict metabolic network properties with particular emphasis on alginate biosynthesis.
- Through novel data mining strategies, identify and rank key markers at the mRNA, protein and metabolite level affecting alginate production.
- Experimentally identify genes not essential for growth that affect alginate biosynthesis using targeted mutagenesis and a genome-saturated transposon insertion library as tools.
- Generate a scientific basis for rational design of strains to be used for future commercialization of microbially produced alginates.
- To identify potential new targets for treatment of Pseudomonas aeruginosa infections in cystic fibrosis patients.
