Development of a kinetics‐integrated CFD model for the industrial scale‐up of DHA fermentation using Schizochytrium sp.

Abstract

In this work, a kinetics-integrated CFD model based on coupling computational fluid dynamics (CFD) and biokinetic was developed to guide the industrial scale-up for fermentation of docosahexaenoic acid (DHA). Two-substrate biokinetic equations for a 5 L bioreactor with oxygen and nitrogen source as limiting substrates were established, which were further coupled with CFD to simulate the biomass growth and lipid accumulation as well as flow field environment in the fermentation process.The coupled CFD-biokinetic model can accurately reflect the changes of each relevant variable in the 50 L bioreactor under different operating conditions. The optimal working conditions of a 35 m 3 bioreactor were predicted by this model and have secured the one-step scale-up of DHA fermentation, resulting in a biomass, lipid concentration, and DHA content in lipids of 99.2 g/L, 55.7 g/L, and 52.5%, respectively.This study thus provides an effective strategy for rapid industrial scale-up of DHA production.

Development of a novel microplate for high‐throughput screening and optimization of DHA producing strains based on CFD technology

“…Yeast, and 30 g L −1 glutamate. [1] Culture experiments in the laboratory were performed in 96-well plates. The strains were inoculated in conventional microtiter plates and novel bioreactors.…”

“…The fermentation medium was artificial seawater containing 70 g L −1 Glu, 1 g L −1 Yeast, and 30 g L −1 glutamate. [ 1 ]…”

“…Over the decades, microorganisms have been used as “mini‐factories” in biomanufacturing to aid in the diversity of metabolic pathways and their accompanying ability to transform a wide range of renewable raw materials into value‐added compounds via fermentation. [ 1–3 ] In the quest to obtain docosahexaenoic acid (DHA) from fish oil, species like Schizochytrium sp. have been widely used in liquid fermentation due to their short growth cycle and high cell density cultivation in bioreactors.…”

“…Over the decades, microorganisms have been used as "mini-factories" in biomanufacturing to aid in the diversity of metabolic pathways and their accompanying ability to transform a wide range of renewable raw materials into value-added compounds via fermentation. [1][2][3] In the quest to obtain docosahexaenoic acid (DHA) from fish oil, species like Schizochytrium sp. have been widely used in liquid fer-Abbreviations: CFD, computational fluid dynamics; DHA, docosahexaenoic acid; ε, average turbulent dissipation rate; Glu, glucose; k, turbulent flow kinetic energy; K L a, oxygen transfer coefficient; MSG, monosodium glutamate; RSM, response surface methodology; Yeast, yeast extract.…”

Optimization and Scale-Up of Fermentation Processes Driven by Models

“…Morchain et al used the EEM to simulate a fermentation process in a 70 L bioreactor and an industrial-scale 70 m 3 bioreactor to explain the performance degradation of industrial bioreactors that mix poorly [ 146 ]. Du et al used the EEM to establish a CFD model coupled with an unstructured kinetic model to explore the effect of bioreactor size and operating conditions on the fermentation process, and they were able to scale-up DHA fermentation from a 5 L bioreactor to a 35 m 3 bioreactor [ 49 ]. Jing et al also built a coupling model to fine-tune the biological production process to a reasonable extent, and they were able to scale-up the production of ferulic acid into vanillin, from shaker to bioreactor, with a conversion rate up to 94% [ 147 ].…”