Filamentous microorganisms are known for their broad spectrum of primary and secondary metabolites. For example, the genus Actinomycetes accounts for over 45% of all known bioactive substances used in the food, pharmaceutical, and agricultural industries[1], such as novel antibiotics or potential chemotherapeutic agents. Despite this potential, the widespread use of filamentous microorganisms is often hindered by inefficient production processes. Filamentous microorganisms grow in a complex mycelial network, and the resulting morphology is not only directly linked to the metabolism responsible for product formation but also causes an increase in the viscosity of the culture broth. The resulting effects of shear-thinning rheology impose limitations on mixing and mass transfer processes, which in turn can lead to growth limitations and metabolic changes. This creates a network of complex interdependencies between rheology and morphology, which complicate effective process development and scaling.
In this project, these interactions will be investigated by varying morphology-controlling parameters (e.g., osmolarity, spore concentration in the inoculum, power input…) in order to develop a comprehensive hybrid model and thereby overcome challenges in process development. Streptomyces coelicolor A(3)2 (S. coelicolor) serves as a model organism for filamentous bacteria and produces two pharmaceutically relevant secondary metabolites: the blue pigment actinorhodin and the red-fluorescent pigment undecylprodigiosin. While actinorhodin exhibits antibiotic activity, undecylprodigiosin offers potential for use as a chemotherapeutic agent or for the treatment of malaria and fungal infections. Following process establishment and optimization in a shake flask, the process will be scaled up to a bioreactor using rheology-based scale-up criteria. Based on the generated data, an integrative hybrid model will then be developed to predict key process parameters and thus ensure effective process development and control.
[1] Correia J, Borges A, Simões M, Simões LC, “Beyond Penicillin: The Potential of Filamentous Fungi for Drug Discovery in the Age of Antibiotic Resistance.” *Antibiotics* 12, 2023, DOI: 10.3390/antibiotics12081250.
