Abstract
Scaling up bioprocesses is one of the most crucial steps in the commercialization of bioproducts. While it is known that concentration and shear rate gradients occur at larger scales, it is often too risky, if feasible at all, to conduct validation experiments at such scales. Using computational fluid dynamics equipped with mechanistic biochemical engineering knowledge of the process, it is possible to simulate such gradients. In this work, concentration profiles for the by-products of baker’s yeast production are investigated. By applying a mechanistic black-box model, concentration heterogeneities for oxygen, glucose, ethanol, and carbon dioxide are evaluated. The results suggest that, although at low concentrations, ethanol is consumed in more than 90% of the tank volume, which prevents cell starvation, even when glucose is virtually depleted. Moreover, long exposure to high dissolved carbon dioxide levels is predicted. Two biomass concentrations, i.e., 10 and 25 g/L, are considered where, in the former, ethanol production is solely because of overflow metabolism while, in the latter, 10% of the ethanol formation is due to dissolved oxygen limitation. This method facilitates the prediction of the living conditions of the microorganism and its utilization to address the limitations via change of strain or bioreactor design or operation conditions. The outcome can also be of value to design a representative scale-down reactor to facilitate strain studies.
Highlights
Bioprocesses are applied for the production of a vast spectrum of commodities, from food and pharmaceuticals to bioplastic and biofuel
Our results indicate that while fluctuations in other concentrations might be experienced by cells on short timescales, the same does not hold true for dCO2, where cells are exposed to high dCO2 for long timescales
This work suggests that in the case of baker’s yeast production, ethanol production is inevitable around the feeding point—in this case, positioned at the top of the vessel
Summary
Bioprocesses are applied for the production of a vast spectrum of commodities, from food and pharmaceuticals to bioplastic and biofuel. Different from their chemical counterparts, transferring promising lab approaches to industrial applications is a major challenge too. Gradients of limiting substrate concentrations, by-products, pH, temperature, and shear rates are formed inevitably. Circulating microorganisms in stirred and gassed large-scale tanks respond to the permanently changing microenvironmental conditions, causing uncertainty of process performance, possibly deteriorating key TRY criteria (titer, rate, yield) [1,2,3,4,5,6]
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