Scale-up of an amoeba-based process for the production of the cannabinoid precursor olivetolic acid.

Autor: Kufs JE; Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI), Jena, Germany., Reimer C; Evolution of Microbial Interactions, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI), Jena, Germany.; Faculty of Biological Sciences, Friedrich Schiller University Jena, Jena, Germany., Steyer E; Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI), Jena, Germany., Valiante V; Biobricks of Microbial Natural Product Syntheses, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI), Jena, Germany., Hillmann F; Evolution of Microbial Interactions, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI), Jena, Germany.; Biochemistry/Biotechnology, Faculty of Engineering, Hochschule Wismar University of Applied Sciences Technology, Business and Design, Wismar, Germany., Regestein L; Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI), Jena, Germany. lars.regestein@leibniz-hki.de.
Jazyk: angličtina
Zdroj: Microbial cell factories [Microb Cell Fact] 2022 Oct 20; Vol. 21 (1), pp. 217. Date of Electronic Publication: 2022 Oct 20.
DOI: 10.1186/s12934-022-01943-w
Abstrakt: Background: The availability of new biological platform organisms to get access to innovative products and processes is fundamental for the progress in biotechnology and bioeconomy. The amoeba Dictyostelium discoideum represents a novel host system that has recently been employed for both the discovery of new natural products and as a cell factory for the production of bioactive compounds such as phytochemicals. However, an essential parameter to evaluate the potential of a new host system is the demonstration of its scalability to allow industrial applicability. Here, we aimed to develop a bioprocess for the production of olivetolic acid, the main precursor of cannabinoids synthesized by a recently engineered D. discoideum strain.
Results: In this study, a sophisticated approach is described to scale-up an amoeba-based polyketide production process in stirred tank bioreactors. Due to the shear sensitivity of the cell wall lacking amoebae, the maximum local energy dissipation rate (ε max ) was selected as a measure for the hydromechanical stress level among different scales. By performing 1.6-L scale batch fermentations with different stress conditions, we determined a maximum tolerable ε max of 3.9 W/kg for D. discoideum. Further, we used this parameter as scale-up criterion to develop a bioprocess for olivetolic acid production starting from a 7-L stirred tank reactor to the industrially relevant 300-L scale with a product concentration of 4.8 µg/L, a productivity of 0.04 µg/L/h and a yield of 0.56 µg/g glucose.
Conclusion: We developed a robust and reliable scale-up strategy for amoeba-based bioprocesses and evaluated its applicability for the production of the cannabinoid precursor olivetolic acid. By determining the maximum tolerable hydromechanical stress level for D. discoideum, we were able to scale-up the process from shake flasks to the 300-L stirred tank reactor without any yield reduction from cell shearing. Hence, we showed the scalability and biotechnological exploitation of amoeba-based processes that can provide a reasonable alternative to chemical syntheses or extractions of phytochemicals from plant biomass.
(© 2022. The Author(s).)
Databáze: MEDLINE
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