An environmental bacterial taxon with a large and distinct metabolic repertoire.

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.

Distribution and diversity of 'Tectomicrobia', a deep-branching uncultivated bacterial lineage harboring rich producers of bioactive metabolites.

Genomic and functional analyses of bacterial sponge symbionts belonging to the uncultivated candidate genus 'Entotheonella' has revealed them as the prolific producers of bioactive compounds previously identified from their invertebrate hosts. These studies also suggested 'Entotheonella' as the first members of a new candidate phylum, 'Tectomicrobia'. Here we analyzed the phylogenetic structure and environmental distribution of this as-yet sparsely populated phylum-like lineage. The data show that 'Entotheonella' and other 'Tectomicrobia' are not restricted to marine habitats but widely distributed among terrestrial locations. The inferred phylogenetic trees suggest several intra-phylum lineages with diverse lifestyles. Of these, the previously described 'Entotheonella' lineage can be more accurately divided into at least three different candidate genera with the terrestrial 'Candidatus Prasianella', the largely terrestrial 'Candidatus Allonella', the 'Candidatus Thalassonella' comprising sponge-associated members, and the more widely distributed 'Candidatus Entotheonella'. Genomic characterization of 'Thalassonella' members from a range of sponge hosts did not suggest a role as providers of natural products, despite high genomic similarity to 'Entotheonella' regarding primary metabolism and implied lifestyle. In contrast, the analysis revealed a correlation between the revised 'Entotheonella' 16S rRNA gene phylogeny and a specific association with sponges and their natural products. This feature might serve as a discovery method to accelerate the identification of new chemically rich 'Entotheonella' variants, and led to the identification of the first 'Entotheonella' symbiont in a non-tetractinellid sponge, Psammocinia sp., indicating a wide host distribution of 'Entotheonella'-based chemical symbiosis.