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.

中文翻译：

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600 m3 气泡塔发酵的真实案例研究：空间分辨模拟揭示了使用大肠杆菌生产 l-苯丙氨酸的优化潜力


大规模发酵 （»100 m³） 经常遇到浓度梯度，这可能会显着影响微生物活性和生产性能。在计算机中可靠地研究此类情况将有助于优化生物生产。但相关模拟非常罕见，尤其是对于大型气泡柱。在这里，我们开创了对 600 m³ 气泡塔的空间分辨率研究，该柱用于基于大肠杆菌的 l-苯丙氨酸补料分批生产。微生物动力学来自实验数据。高级欧拉-拉格朗日 （EL） 计算流体动力学 （CFD） 仿真用于跟踪最近开发的气泡破裂模型产生的单个气泡动力学。在此基础上，对流体动力学、传质和微生物活动的复杂非线性特征进行了大规模模拟，并与真实数据进行了比较。作为一个关键特征，确定了主导混合和传质的上升管、下降管和循环单元区域。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分成多个部分。因此，将不同位置的两种进料分成两个进料的实际进料率来评估替代进料设计。相反的反向安装进料点和喷射器使产品合成提高了 6.24%，而替代情景使增长率提高了 11.05%。结果表明，复杂的空间分辨流体动力学、传质和微生物动力学模拟如何帮助优化计算机模拟中的生物反应器。