Effects of particle addition to Streptomyces cultivations to optimize the production of actinorhodin and streptavidin

D. Holtmann, F. Vernen, J. M. Müller, D. Kaden, J. M. Risse, K. Friehs, L. Dähne, A. Stratmann, J. Schrader

Streptomyces is a genus of Gram-positive bacteria that grow in various environments, and its shape resembles filamentous fungi. The most interesting property of Streptomyces is the ability to produce bioactive secondary metabolites, such as antifungals, antivirals, antitumorals, and especially antibiotics. In submersed culture Streptomyces and other filamentous microorganisms can grow as free mycelium, pellets or intermediate growth forms. All growth forms can be beneficial for product formation depending on the microbial strain and the product of interest. Here, the effects of addition of particles on the growth and product formation of two Streptomyces strains were investigated. Streptomyces coelicolor was used as a model organism for the production of the antibiotic actinorhodin and Streptomyces avidinii was used to produce streptavidin. In all experiments, the addition of broken and porous SiO2 particles (120–200 µm) to the culture medium led to an increased productivity. In order to evaluate the particle effect on actinorhodin production three different media with and without the addition of particles were compared. The productivity was strongly influenced by the choice of media and was further improved by the addition of particles. The enhancement factor between un-supplemented and supplemented cultures varied between 85% by using a complex medium and 160% in a minimal medium. The highest product concentration of 855 mg actinorhodin L−1 was measured after 12 days in a complex medium by addition of 5 g glass particles L−1. In contrast, the final concentration of streptavidin was not affected by the supplementation of glass beads (diameter: 0.25–0.5 mm) to cultures of Streptomyces avidinii. Nevertheless, a kinetic effect occurred upon supplementation by particles, allowing an acceleration of product formation. The impact of the particle addition to the Streptomyces cultures on the sustainability of the bioprocess was proven by using the E-factor. The E-factor denotes the amount of waste generated per product equivalent. This evaluation shows the beneficial effects of the particle addition in both production systems. Due to the fact that the particle addition leads to a decreased E-factor a life cycle assessment should be performed to further evaluate the particle effect on the sustainability of the complete process chain.

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