文献类型：期刊文献

英文题名：Integration of microbial kinetics and fluid dynamics toward model-driven scale-up of industrial bioprocesses

作者：Wang, Guan[1]; Tang, Wenjun[1]; Xia, Jianye[1]; Chu, Ju[1]; Noorman, Henk[2]; van Gulik, Walter M.[3]

机构：[1] State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China; [2] DSM Biotechnology Center, Delft, Netherlands; [3] Department of Biotechnology, Kluyver Centre for Genomics of Industrial Fermentation, Delft University of Technology, Delft, Netherlands

年份：2020

卷号：15

期号：1

起止页码：20

外文期刊名：Engineering in Life Sciences

收录：EI(收录号：20150100400398)

语种：英文

外文关键词：Metabolism - Mass transfer - Mixing - Metabolic engineering - Batch data processing - Kinetics - Carbon dioxide

摘要：Scale-up of bioprocesses is hampered by open questions, mostly related to poor mixing and mass transfer limitations. Concentration gradients of substrate, carbon dioxide, and oxygen in time and space, especially in large-scale high-cell density fed-batch processes, are likely induced as the mixing time of the fermentor is usually longer than the relevant cellular reaction time. Cells in the fermentor are therefore repeatedly exposed to dynamic environments or perturbations. As a consequence, the heterogeneity in industrial practices often decreases either yield, titer, or productivity, or combinations thereof and increases by-product formation as compared to well-mixed small-scale bioreactors, which is summarized as scale-up effects. Identification of response mechanisms of the microorganism to various external perturbations is of great importance for pinpointing metabolic bottlenecks and targets for metabolic engineering. In this review, pulse response experimentation is proposed as an ideal way of obtaining kinetic information in combination with scale-down approaches for in-depth understanding of dynamic response mechanisms. As an emerging tool, computational fluid dynamics is able to draw a holistic picture of the fluid flow and concentration fields in the fermentor and finds its use in the optimization of fermentor design and process strategy. In the future, directed strain improvement and fermentor redesign are expected to largely depend on models, in which both microbial kinetics and fluid dynamics are thoroughly integrated. ? 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.