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Akronym
StrepBio2Films
Projekt Titel
Streptomyces bioFilms - Biosynthesis, composition and their potential as productive systems in tubular Bioreactors
Förderkennzeichen
HE 8503/3-1
Funding code
945.945.03-023
Startdatum
September 1, 2025
Enddatum
August 31, 2028
Gepris ID
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Funder
Deutsche Forschungsgemeinschaft
Streptomyces are considered as ‘biofactories’ of secondary metabolites and are therefore extensively used in industrial biotechnology for the production of compounds with important biological activities in medicine, food industry and agronomy. These bacteria are prominent members of the soil microbiome with a fascinating developmental biology involving a complex transition from filaments to spores. In industrial bioprocesses they are mostly cultivated in large scale stirred-tank bioreactors as planktonic cells. However, because of their filamentous nature, maintaining optimal cultivation conditions for high productivity is often challenging due to the formation of cell clumps. In their natural habitat soil, Streptomyces exist in biofilms, but little is known about the formation, composition and regulation of biofilms in this genus. Moreover, the experience with Streptomyces biofilms for production of antibiotics in bioreactors is also extremely limited. In this interdisciplinary proposal, the synergetic combination of a molecular microbiologist and an expert in bioprocess engineering provides a unique possibility to study the mechanisms of biofilm formation in Streptomyces and additionally get important insights about robustness, responsiveness and productivity of these biofilms in bioreactors especially in response to bioprocess gradients of different kind. As Streptomyces physiology is diverse, to advance our knowledge about biofilm formation and composition, we will study different Streptomyces models (S. venezuelae, S. griseus and S. coelicolor) for antibiotics production and build on our preliminary data showing that in S. venezuelae c-di-GMP induces extracellular matrix (ECM) formation through a novel matrix synthase complex. We will isolate the extracellular matrix and analyze its composition and biophysical properties and investigate how antibiotic titers are affected by the ECM. We plan to achieve a breakthrough in Streptomyces application as cell factories and will establish two millilitre scale 3D-printed tubular flow bioreactor setups for productive Streptomyces biofilms to analyse how different bioprocess gradients in vertical and horizontal direction affect biofilm robustness, productivity and physiology on population and single cell level. For that purpose, we will analyse key performance parameters but also apply fluorescent reporter strain, whose fluorescence will be monitored via fluorescence microscopy and omics analysis. Altogether, our combined complementary expertise and strong preliminary data represent a powerful and unique baseline for understanding and application of Streptomyces biofilms for production of antibiotics with the aim to increase productivity of industrially important drugs for human benefits.