Synergistically applying 1-D modeling and CFD for designing industrial scale bubble column syngas bioreactors.

The reduction of greenhouse gas emissions and future perspectives of circular economy ask for new solutions to produce commodities and fine chemicals. Large-scale bubble columns operated by gaseous substrates such as CO, CO2, and H2 to feed acetogens for product formations could be promising approaches. Valid in silico predictions of large-scale performance are needed to dimension bioreactors properly taking into account biological constraints, too. This contribution deals with the trade-off between sophisticated spatiotemporally resolved large-scale simulations using computationally intensive Euler-Euler and Euler-Lagrange approaches and coarse-grained 1-D models enabling fast performance evaluations. It is shown that proper consideration of gas hold-up is key to predict biological performance. Intrinsic bias of 1-D models can be compensated by reconsideration of Sauter diameters derived from uniquely performed Euler-Lagrange computational fluid dynamics.

Lagrangian Trajectories to Predict the Formation of Population Heterogeneity in Large-Scale Bioreactors.

Successful scale-up of bioprocesses requires that laboratory-scale performance is equally achieved during large-scale production to meet economic constraints. In industry, heuristic approaches are often applied, making use of physical scale-up criteria that do not consider cellular needs or properties. As a consequence, large-scale productivities, conversion yields, or product purities are often deteriorated, which may prevent economic success. The occurrence of population heterogeneity in large-scale production may be the reason for underperformance. In this study, an in silico method to predict the formation of population heterogeneity by combining computational fluid dynamics (CFD) with a cell cycle model of Pseudomonas putida KT2440 was developed. The glucose gradient and flow field of a 54,000 L stirred tank reactor were generated with the Euler approach, and bacterial movement was simulated as Lagrange particles. The latter were statistically evaluated using a cell cycle model. Accordingly, 72% of all cells were found to switch between standard and multifork replication, and 10% were likely to undergo massive, transcriptional adaptations to respond to extracellular starving conditions. At the same time, 56% of all cells replicated very fast, with µ ≥ 0.3 h-1 performing multifork replication. The population showed very strong heterogeneity, as indicated by the observation that 52.9% showed higher than average adenosine triphosphate (ATP) maintenance demands (12.2%, up to 1.5 fold). These results underline the potential of CFD linked to structured cell cycle models for predicting large-scale heterogeneity in silico and ab initio.