Scale‐up of Streptomyces species cultivations based on the morphological response to the energy dissipation rate

Filamentous microorganisms exhibit complex morphologies that influence product formation and are affected by various bioprocess parameters. Consistent morphology is therefore essential for comparable results during scale‐up. This study investigates the scale‐up of Streptomyces species ( Streptomyces spp.) cultivations from shake flasks to stirred‐tank reactors while maintaining comparable morphology. Shake flask cultivations demonstrated that variations in hydromechanical stress, quantified by the energy dissipation rate, strongly affect the morphology of Streptomyces spp., confirming its relevance for scale‐up. A scale‐up based on the average energy dissipation rate led to altered morphology. Alternatively, the maximum energy dissipation rate was investigated, as it reflects hydromechanical stress more accurately. Since prior determination or measurement is unfeasible, computational fluid dynamics (CFD) simulations were applied for systematic quantification. Scale‐up based on these simulations resulted in improved morphological consistency across scales, suggesting a new scale‐up parameter. To overcome oxygen limitations, pure oxygen aeration was implemented, further enhancing morphological comparability.