title: Polytheonamide biosynthesis showcasing the metabolic potential of sponge-associated uncultivated 'Entotheonella' bacteria.
abstract: The vast majority of microorganisms on the planet have not been grown under laboratory conditions due to unknown metabolic and environmental constraints. This uncultivated majority has enormous potential as a reservoir of unique enzymology and biosynthetic pathways. The following review offers a glimpse into this unexplored enzymatic stockpile through recent progress made on the biosynthesis of the potent polytheonamide cytotoxins. These structurally highly complex pore-forming peptides, isolated from the marine sponge Theonella swinhoei, are synthesized by the ribosome and then modified through numerous unusual transformations including iterative epimerase and N-methyltransferase activities. The bacterial source of these metabolites was identified as the taxonomically remote, uncultivated sponge symbiont 'Entotheonella factor' with a biosynthetic prowess that rivals those of industrially exploited microorganisms.
authors.affiliation: Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Freeman
authors.affiliation: Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Vagstad
authors.affiliation: Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland. Electronic address: jpiel@ethz.ch.
authors.forename: Jörn
authors.initials: J
authors.lastname: Piel
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D014176:Protein Biosynthesis; D047232:Theonella / Q000378:metabolism* / Q000382:microbiology