The microbial community of the freshwater sponge Spongilla lacustris collected in an Austrian lake was investigated using both culture-dependent and -independent methods. Representatives of 41 bacterial genera were isolated from the sponge sample and classified according to their 16S rRNA gene sequences. Genomes of 33 isolates were sequenced and analyzed for the presence of secondary metabolite biosynthesis gene clusters (BGCs), demonstrating a significant biosynthetic potential. Metagenome and 16S rRNA gene amplicon analyses revealed very little overlap between the cultivated and environmental bacteria, and yielded 20 metagenome-assembled genomes (MAGs) most of which harbored several BGCs. Activation of a cryptic BGC in Streptomyces isolates resulted in the production of naphthoquinone alkaloids coprisidins.