Cultivated bacteria such as actinomycetes are a highly useful source of biomedically important natural products. However, such `talented' producers represent only a minute fraction of the entire, mostly uncultivated, prokaryotic diversity. The uncultured majority is generally perceived as a large, untapped resource of new drug candidates, but so far it is unknown whether taxa containing talented bacteria indeed exist. Here we report the single-cell- and metagenomics-based discovery of such producers. Two phylotypes of the candidate genus `Entotheonella' with genomes of greater than 9 megabases and multiple, distinct biosynthetic gene clusters co-inhabit the chemically and microbially rich marine sponge Theonella swinhoei. Almost all bioactive polyketides and peptides known from this animal were attributed to a single phylotype. `Entotheonella' spp. are widely distributed in sponges and belong to an environmental taxon proposed here as candidate phylum `Tectomicrobia'. The pronounced bioactivities and chemical uniqueness of `Entotheonella' compounds provide significant opportunities for ecological studies and drug discovery.