Effects of growth medium conditions on antibiotic production by actinomyces sp.

Ramoplanin antibiotic has been shown to be the most effective to treat the bacteria that cause hospital infections even at low minimum inhibitory concentrations. However, the main obstacle for this antibiotic is its quite expensive cost. Due to preferred techniques in the antibiotic production require long-term optimizations, these techniques cause increasing production cost and period. To overcome shortcomings, metabolisms of industrially important microorganisms are examined by approaching to stoichiometric modeling and data analysis of integrated systems-based. For this purpose, it is started to research which is carried out computerized stoichiometric modeling that allows identification and regulation of metabolic flows within microorganism cells. In this project, computerized stoichiometric modeling with MATLAB and COPASI software packages will be used for decrease to production cost of ramoplanin which is the most effective but very expensive in available antibiotics. In the thesis, in order to identify the aspects of intermediary metabolism relevant to ramoplanin production, the correlation between ramoplanin antibiotic production and intracellular tricarboxylic acid cycle (TCA) intermediate products were investigated depending on the glucose concentration and nitrogen sources of Actinoplanes sp. ATCC 33076 medium by using both the computerized stoichiometric modeling and experimental conditions. The flux balance analysis optimisation, using either growth or antibiotic production as objective function, did not correlate with experimental ramoplanin yields in fed processes since the maximum ramoplanin production of stoichiometric modeling and experimental conditions were determined at 5 and 10g g/L glucose, respectively. The diferences suggest that candidate process feed nutrients that might be expected to influence this network were used in process simulations and in silico predictions compared to experimental findings. Therefore, in this kind of study, experiments should be done and data of computerized stoichiometric modeling should be compared.