600 立方米气泡塔发酵的真实案例研究:空间分辨模拟揭示大肠杆菌生产 l-苯丙氨酸的优化潜力

IF 3.5 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnology and Bioengineering Pub Date : 2024-10-25 DOI:10.1002/bit.28869
Yannic Mast, Adel Ghaderi, Ralf Takors
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引用次数: 0

摘要

大规模发酵("100 m³")经常会遇到浓度梯度,这可能会严重影响微生物的活动和生产性能。对这种情况进行可靠的模拟研究可以优化生物生产。但相关模拟非常罕见,尤其是针对大型气泡塔的模拟。在此,我们率先对一个 600 立方米的气泡塔进行了空间分辨研究,该气泡塔以大肠杆菌为基础,进行间歇式苯丙氨酸生产。微生物动力学源于实验数据。先进的欧拉-拉格朗日(EL)计算流体动力学(CFD)模拟用于跟踪最近开发的气泡破裂模型所产生的单个气泡动力学。由此,对流体动力学、传质和微生物活动的复杂非线性特性进行了大规模模拟,并与实际数据进行了比较。作为一个关键特征,确定了主导混合和传质的上行器、下行器和循环池区域。这导致葡萄糖、溶解氧和微生物速率的复杂梯度,将生物反应器划分为不同的区域。因此,我们对替代进料设计进行了评估,在不同位置将实际进料率分成两个进料点。相反,反向安装进料点和喷射器可将产品合成率提高 6.24%,而交替方案可将生长率提高 11.05%。这些结果表明,对流体力学、传质和微生物动力学进行复杂的空间分辨模拟,有助于在硅学中优化生物反应器。
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Real Case Study of 600 m3 Bubble Column Fermentations: Spatially Resolved Simulations Unveil Optimization Potentials for l-Phenylalanine Production With Escherichia coli
Large-scale fermentations (»100 m³) often encounter concentration gradients which may significantly affect microbial activities and production performance. Reliably investigating such scenarios in silico would allow to optimize bioproduction. But related simulations are very rare in particular for large bubble columns. Here, we pioneer the spatially resolved investigation of a 600 m³ bubble column operating for Escherichia coli based l-phenylalanine fed-batch production. Microbial kinetics are derived from experimental data. Advanced Euler-Lagrange (EL) computational fluid dynamics (CFD) simulations are applied to track individual bubble dynamics that result from a recently developed bubble breakage model. Thereon, the complex nonlinear characteristics of hydrodynamics, mass transfer, and microbial activities are simulated for large scale and compared with real data. As a key characteristic, zones for upriser, downcomer, and circulation cells were identified that dominate mixing and mass transfer. This results in complex gradients of glucose, dissolved oxygen, and microbial rates dividing the bioreactor into sections. Consequently, alternate feed designs are evaluated splitting real feed rates in two feeds at different locations. The opposite reversed installation of feed spots and spargers improved the product synthesis by 6.24% while alternate scenarios increased the growth rate by 11.05%. The results demonstrate how sophisticated, spatially resolved simulations of hydrodynamics, mass transfer, and microbial kinetics help to optimize bioreactors in silico.
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来源期刊
Biotechnology and Bioengineering
Biotechnology and Bioengineering 工程技术-生物工程与应用微生物
CiteScore
7.90
自引率
5.30%
发文量
280
审稿时长
2.1 months
期刊介绍: Biotechnology & Bioengineering publishes Perspectives, Articles, Reviews, Mini-Reviews, and Communications to the Editor that embrace all aspects of biotechnology. These include: -Enzyme systems and their applications, including enzyme reactors, purification, and applied aspects of protein engineering -Animal-cell biotechnology, including media development -Applied aspects of cellular physiology, metabolism, and energetics -Biocatalysis and applied enzymology, including enzyme reactors, protein engineering, and nanobiotechnology -Biothermodynamics -Biofuels, including biomass and renewable resource engineering -Biomaterials, including delivery systems and materials for tissue engineering -Bioprocess engineering, including kinetics and modeling of biological systems, transport phenomena in bioreactors, bioreactor design, monitoring, and control -Biosensors and instrumentation -Computational and systems biology, including bioinformatics and genomic/proteomic studies -Environmental biotechnology, including biofilms, algal systems, and bioremediation -Metabolic and cellular engineering -Plant-cell biotechnology -Spectroscopic and other analytical techniques for biotechnological applications -Synthetic biology -Tissue engineering, stem-cell bioengineering, regenerative medicine, gene therapy and delivery systems The editors will consider papers for publication based on novelty, their immediate or future impact on biotechnological processes, and their contribution to the advancement of biochemical engineering science. Submission of papers dealing with routine aspects of bioprocessing, description of established equipment, and routine applications of established methodologies (e.g., control strategies, modeling, experimental methods) is discouraged. Theoretical papers will be judged based on the novelty of the approach and their potential impact, or on their novel capability to predict and elucidate experimental observations.
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