An environmental bacterial taxon with a large and distinct metabolic repertoire

Abstract

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. Single-cell- and metagenomics-based study reveals two members of the candidate genus ‘Entotheonella’, symbionts of the marine sponge Theonella swinhoei; distinct biosynthetic gene clusters that account for most of the bioactive polyketides and peptides known from T. swinhoei are shown to be attributable to a single member of the T. swinhoei Y microbiome. Almost all drugs and drug candidates from bacteria are produced by a few groups of metabolically rich organisms. That leaves the unculturable — or uncultivated — microbial majority as a largely untapped resource. Here Jörn Piel and colleagues report the use of single-cell and metagenomic analysis to identify two potential 'environmental factories', both members of the candidate genus Entotheonella and symbionts of the chemically rich marine sponge Theonella swinhoei. Importantly they find that the genomes of both microbes encode multiple distinct biosynthetic gene clusters that together account for most of the bioactive polyketides and peptides previously thought to be produced by the sponge host. This discovery identifies Entotheonella and members of the newly proposed phylum Tectomicrobia as a 'biochemically talented' phylum on a par with the actinomycetes.