Dynamic modeling and control of the main metabolism in Lactic acid bacteria
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School of Science |
Master's thesis
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Date
2013
Department
Major/Subject
Informaatiotekniikka
Mcode
T-61
Degree programme
Language
en
Pages
62
Series
Abstract
Lactic acid bacteria (LAB) are widely used in industrial manufacture of fermented foods and regarded as cell factories for production of pharmaceutical and food products. Lactococcus lactis, due to its small genome size and simple metabolism, has been considered a model organism for strain design strategies and metabolic engineering. Metabolic modelling provides a platform to conduct in silico experiments with biotechnological and biomedical applications. With a fully detailed kinetic model, time-course simulations, response to different input can be predicted and system controllers can be designed. For L. lactis, the dynamic models for the central carbon metabolism have already been constructed. However, these models lack our compound of interest and need to be extended. Provided the topology of pathway and kinetic parameters, a dynamic model that describes the glycolytic pathway in L. lactis is reconstructed using convenience kinetics. This model is now improved by estimating the parameters using in vivo Nuclear Magnetic Resonance (NMR) data fitting. Sensitivity analysis was performed in the reconstructed model for acetoin and butanediol production which suggests that down expression of the enzyme levels for lactate dehydrogenase, phosphofructokinase, pyruvate dehydrogenase causes a rise in production of acetoin and 2,3-butanediol. In addition to these enzyme levels, down expression of acetoin transportase and alcohol dehydrogenase levels accounts for enhanced production of 2,3-butanediol. The reconstructed model can be used as a basis to design metabolic engineering experiments and also to predict the phenotype of the bacterium under different environmental and genetic conditions. The model can also serve as a starting point to model other LAB for instance Streptococcus pneumoniae.Description
Supervisor
Rousu, Juho|Sa-Correia, IsabelThesis advisor
Sousa Costa, RafaelKeywords
Lactococcus lactis, dynamic modeling, parameter estimation, convenience kinetics, in vivo NMR data fitting, sensitivity control analysis