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

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.