A 9‐pool metabolic structured kinetic model describing days to seconds dynamics of growth and product formation by Penicillium chrysogenum. Issue 8 (18th May 2017)

• Record Type: Journal Article
• Authors: Tang, Wenjun; Deshmukh, Amit T.; Haringa, Cees; Wang, Guan; van Gulik, Walter; van Winden, Wouter; Reuss, Matthias; Heijnen, Joseph J.; Xia, Jianye; Chu, Ju; Noorman, Henk J.
• Is Part Of: Biotechnology and bioengineering. Volume 114:Issue 8(2017)
• Page Start: 1733
• Page End: 1743
• Publication Date: 2017-05-18
• Subjects: structured model -- black box model -- feast–famine -- kinetics -- Penicillium chrysogenum; Biotechnology -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/bit.26294
• Languages: English
• ISSNs: 0006-3592

Abstract

ABSTRACT: 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. © 2017 Wiley Periodicals, Inc. Abstract : A structured kinetic model of P. chrysogenum for growth and production is presented based on 4 enzyme pools, 5 lumped metabolite pools, and 10 reactions. The result showed its capability in predicting strain performance in steady states and dynamics from the second to day timescale. Glucose starvation condition was successfully described through alternative intracellular carbon source, including the productivity lost under feast–famine regime. Its relatively simple structure and low computation requirement enables its further integration in CFD framework.