Influence of Cellulose Particles on Streptomyces spp. Growth, Morphology, and Metabolite Spectrum

Filamentous soil bacteria of the genus Streptomyces are a major source of bioactive natural products, including antibiotics. However, their industrial cultivation is complicated by complex morphologies ranging from dispersed mycelia to dense pellets, which are closely linked to productivity. Microparticles, such as talc or aluminium oxide, are commonly added to modulate macromorphology, yet their effects across diverse Streptomyces species remain insufficiently characterized. Here, we systematically evaluated the impact of cellulose particles on growth, morphology, and metabolite production in 13 Streptomyces species (Streptomyces spp.). Cellulose addition significantly reduced pellet size and altered metabolite profiles in a species-dependent manner, resulting predominantly in a decrease of natural product abundance. Without cellulose addition, metabolite profiles correlated with biosynthetic potential encoded in the genomes, whereas this relationship did not hold in the presence of cellulose. With the addition of cellulose, a decrease in peptide signals present across species was observed. Cellulose-associated mechanical stress led to species-specific metabolomic shifts characterized by increased amino acids, lipids, and other degradation products, consistent with enhanced mechanical cellular disruption, which might have decreased proteolytic turnover during the stationary phase in some species that were more prone to mechanical stress. Although pellet size reduction is often associated with increased abundance of natural products, these findings demonstrate that the influence of solid particles on Streptomyces natural products and metabolism is species-dependent. This work provides a foundation for future studies using dynamic systems, such as co-cultivation with cellulolytic organisms, to improve natural product discovery.