Research For The Modeling Of Penicillium Chrysogenum Fed-Batch Fermentation Process

Penicillin is the first antibiotic found in history. It initiates a new age of antibiotic treatment and is still widely used in clinic. Accompanying with the birth of penicillin, microorganism fermentation has become a major part of pharmaceutical industry from then on. Aiming at the real process of industrial penicillin fermentation, the following aspects are focused on:1. Research of the metabolic network of Penicillium chrysogenum in fed-batch fermentationThe major three metabolic pathways existing in the common organisms, including glycolysis, TCA cycle, as well as the oxidative phosphorylation pathways, are illustrated. Research into the metabolic network of complex penicillin fed-batch fermentation and analyze the main metabolic pathways in the metabolic network, as well as the nitrogen metabolism.2. Research of the biological fermentation modelThe development of modeling of biological fermentation process is retrospected, from the original unstructured model to structured model, then to the cybernetic model. For the unstructured model, the cell is considered as a whole and the behavior is cosistent. In the unstructured model, the reactions take place in the cell are not considered. The structured model is a kind of mechanism model, what it concern is the metabolic pathways and the corresponding chemical reactions. According to the established stoichiometric balance model, cell growth is described. Cybernetic model, belonging to the gray model, on the basis of the analyzed metabolic network, solve the unknown variables through the known variables. While, in the practically industrial process, some variable are not mesearable, and these variables can not be used to the validation of the model.3. Cybernetic model of the penicillin fermentation processAccording to the modeling steps and framework of cybernetic approach, on the basis of the proposed metabolic network of penicillin in the literature, the abstracted metabolic pathway of penicillin is derived. The industrial data are used to validate the model.4. DiscussionTaking the myeloma cell as the example of animal cell, the establishing approach of cybernetic model for the animal cell is discussed. Similar to the penicillin modeling method, the abstracted myeloma cell metabolic network also includes three metabolic pathway.