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Particle based Cultivation of Lentzea aerocolonigenes in Membrane aerated stirred Bioreactors for increased Rebeccamycin Production

Schrinner, Kathrin GND; Schrader, Marcel GND; Niebusch, Jana; Wurzler, Nadine; Kwade, Arno GND; Krull, Rainer GND

Filamentous microorganisms represent the majority of natural producers of antibiotics and other active pharmaceutical ingredients (APIs). Lentzea aerocolonigenes is a filamentous actinomycete producing the antitumor antibiotic rebeccamycin. The addition of glass beads (100 g/L, ⌀ = 969 μm) in shake flask cultivations led to a significant increase in rebeccamycin production compared to an unsupplemented cultivation by inducing mechanical stress. To achieve larger amounts of rebeccamycin a scale-up was conducted. A bubble free membrane aeration was chosen to reduce the power input to stirrer and particle induced stress. Glass bead addition (50 g/L, ⌀ = 969 μm) in this membrane aerated stirred bioreactor increased rebeccamycin concentration compared to an unsupplemented cultivation as well. Moreover it reduced biomass growth on the aeration membrane which is a widespread challenge in membrane aerated bioreactors.

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