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Filamentous fungi, pressurized bioprocess, overpressure

Abstract

Aerobic microbial bioprocesses are indispensable for producing many biotechnological products. Due to the low solubility of oxygen, this essential substrate needs to be constantly supplied during bioprocesses. Filamentous fungi can form diverse morphologies from dispersed mycelia to dense pellets in  liquid cultures (Cox et al., 1998). Especially, freely dispersed growth often increases the culture broth viscosity resulting in mixing problems accompanied by extremely reduced air bubble dispersion and inhomogeneous nutrient supply. Moreover, the shear sensitivity of filamentous structures can limit  stirrer speed adaptations to counteract mixing issues. Besides aeration rate, bubble dispersion, and aeration with elevated oxygen concentrations, overpressure is a measure to generally increase gas solubilities, and thus, gas transfer (Knoll et al., 2007). Therefore, the application of overpressure  presents a promising strategy to overcome oxygen limitation without the need for increased stirrer speeds for filamentous fungi.

At Leibniz-HKI, the filamentous fungus Aspergillus nidulans was genetically modified for heterologous production of psilocybin, a promising prodrug candidate in psychotherapy (Hoefgen et al., 2018). To maximize psilocybin formation, the influence of hydromechanical stress and the application of  overpressure on growth and product formation were investigated in 7 l stirred tank reactors and 7.5 l pressure reactors. Within the tested conditions, increasing stirrer speeds correlated with a process time reduction. The pressurization further shortened process time and enabled oxygen-unlimited  cultivation at reduced hydromechanical stress.

Acknowledgement

This work was supported by a grant from the European Social Fund ESF “Europe for Thuringia” project HoWi (2019FGR0079, LR, BB, JK and SW). The authors thank Gudrun Krauter, Patrick Berthel, Michael Cyrulies, and Michael Meyer for their helpful technical support during fermentations and analytics.

References

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