文献类型：期刊文献

英文题名：A 9-pool metabolic structured kinetic model describing days to seconds dynamics of growth and product formation by Penicillium chrysogenum

作者：Tang, Wenjun[1];Deshmukh, Amit T.[2];Haringa, Cees[3];Wang, Guan[1];van Gulik, Walter[3];van Winden, Wouter[2];Reuss, Matthias[4];Heijnen, Joseph J.[3];Xia, Jianye[1];Chu, Ju[1];Noorman, Henk J.[2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, POB 329,130 Meilong Rd, Shanghai, Peoples R China;[2]DSM Biotechnol Ctr, Delft, Netherlands;[3]Delft Univ Technol, Dept Biotechnol, Cell Syst Engn, Delft, Netherlands;[4]Univ Stuttgart, Inst Biochem Engn, Stuttgart, Germany

年份：2017

卷号：114

期号：8

起止页码：1733

外文期刊名：BIOTECHNOLOGY AND BIOENGINEERING

收录：;EI(收录号：20172603848403);WOS:【SCI-EXPANDED(收录号:WOS:000404130200010)】；

基金：Contract grant sponsor: Netherlands Organisation for Scientific Research Contract grant sponsor: Ministry of Science and Technology of the People's Republic of China Contract grant number: 2013DFG32630

语种：英文

外文关键词：structured model; black box model; feast-famine; kinetics; Penicillium chrysogenum

摘要：A powerful approach for the optimization of industrial bioprocesses is to perform detailed simulations integrating large-scale computational fluid dynamics (CFD) and cellular reaction dynamics (CRD). However, complex metabolic kinetic models containing a large number of equations pose formidable challenges in CFD-CRD coupling and computation time afterward. This necessitates to formulate a relatively simple but yet representative model structure. Such a kinetic model should be able to reproduce metabolic responses for short-term (mixing time scale of tens of seconds) and long-term (fed-batch cultivation of hours/days) dynamics in industrial bioprocesses. In this paper, we used Penicillium chrysogenum as a model system and developed a metabolically structured kinetic model for growth and production. By lumping the most important intracellular metabolites in 5 pools and 4 intracellular enzyme pools, linked by 10 reactions, we succeeded in maintaining the model structure relatively simple, while providing informative insight into the state of the organism. The performance of this 9-pool model was validated with a periodic glucose feast-famine cycle experiment at the minute time scale. Comparison of this model and a reported black box model for this strain shows the necessity of employing a structured model under feast-famine conditions. This proposed model provides deeper insight into the in vivo kinetics and, most importantly, can be straightforwardly integrated into a computational fluid dynamic framework for simulating complete fermentation performance and cell population dynamics in large scale and small scale fermentors. Biotechnol. Bioeng. 2017;114: 1733-1743. (c) 2017 Wiley Periodicals, Inc.