Black box kinetic modeling of growth and citric acid production by Candida oleophila ATCC20177

Mathematical modeling allows representation of biological systems, explanation of underlying mechanisms and prediction of system behavior. As such, it is one of the key focus points for both fundamental and applied research not only to improve our understading, but also to decrease costs by reducing the necessary experiments. Organic acids are used in several industries, such as monomers for bioplastics, food preservatives and additives, pharmaceuticals, agriculture etc. Non-petrochemical, sustainable production of these acids is of great interest which can be achieved by fermentation of cheap substrates into various organic acids. The desired form of these typically weak acids is the protonated form (HA), to decrease the overall production and downstream costs. This form can be obtained by fermentation at the pH below the pKa of the corresponding acid. In production of organic acid, key is to determine growth and acid production dynamics, as the product itself has direct and indirect intibitory effects on the host. The aim of this thesis, is to set up and analyze a mathematical model to study the dynamics of the growth and production of citric acid by building a black-box kinetic model using published batch fermentation data. Noncompetitive inhibition on substrate uptake reflected the system dynamics better than the competitive inhibition model. Monte Carlo study is also carried to find possible correlations among parameters. Glucose saturation constants were not correlated to their respective maximum specific growth rates. Parameters related to the energetics of growth and production are also determined as growth (Kx) and non growth associated (mATP) maintenance constants. The 90 per cent confidence intervals of Kx and mATP were [0.6, 4] and [2.5, 8] respectively for published P/O ratio of 1.45. Also at dilution rates lower than 0.07 h-1, the obtained model reflected well the experimentally reported changes in chemostat.