Study On Dynamic Metabolic Model For Citric Acid Fermentation By Aspergillus Niger

Citric acid has the largest demand among organic acid in the world,which is widely applied in food industry、pharmaceutical industry andchemical industry. China is the most important country in citric acidproduction and exportation. Aspergillus niger is commonly used forindustrial citric acid and also an important industrial microorganism witha potential to become cellular factory, which arouse researchers’extensive interest to disclose its mechanism.In this thesis, the metabolic network in Aspergillus niger isinvestigated by integrating ‘omics’ information and bibliome. Asimplified metabolic network is set up. Based on stoichiometric balancein the simplified metabolic network, a model describing the balance ofintracellular substances and energy flow rates is constructed. Meanwhile,a first-order closed-loop regulator model is used to describe the inductionof the enzyme pool shortly after inoculation. These models are thencoupled with a bioreactor model so that metabolic fluxes and key statevariables, such as substrate concentration and product concentrationbecome calculable. Differential Evolution was applied for model parameter identification. Model validation result is presented, whichdemonstrate that the model can describe the substrate uptake and citricacid production with reasonable accuracy. Changes in metabolic fluxshow the cellular mechanism of citric acid accumulation. Besides, anunstructured model is constructed as part of preliminary work.Phenomenon of hydrolysis and transportation process is studied andcorresponding mathematic model is presented as supplement. Onlineestimation and prediction methods are discussed and an online productionconcentration estimation approach is presented.