title: Cyanobacterial ent-Sterol-Like Natural Products from a Deviated Ubiquinone Pathway.
abstract: Natural products from marine animals show high potential for the development of new medicines, but drug development based on these compounds is commonly hampered by their low natural abundance. Since many of these metabolites are suspected or known to be produced by uncultivated bacterial symbionts, the rapidly growing diversity of sequenced prokaryotic genomes offers the opportunity to identify alternative, culturable sources of natural products computationally. In this work, we investigated the potential of using this sequenced resource to facilitate the production of meroterpenoid-like compounds related to those from marine sources. This genome-mining strategy revealed a biosynthetic gene cluster for highly modified cytotoxic meroterpenoids related to pelorol and other compounds isolated from sponges. Functional characterization of the terpene cyclase MstE showed that it generates an ent-sterol-like skeleton fused to an aryl moiety from an open-chain precursor and is therefore a promising tool for the chemoenzymatic preparation of synthetically challenging chemical scaffolds.
authors.affiliation: Institut für Mikrobiologie, Eidgenössiche Technische Hochschule (ETH) Zürich, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Moosmann
authors.affiliation: Institut für Mikrobiologie, Eidgenössiche Technische Hochschule (ETH) Zürich, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ueoka
authors.affiliation: Dipartimento di Farmacia Università di Napoli Federico II, Università di Napoli Federico II, via D. Montesano 49, 80131, Napoli, Italy.|Current address: Stazione Zoologica Anton Dohrn, Villa Comunale, 80121, Napoli, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Grauso
authors.affiliation: Dipartimento di Farmacia Università di Napoli Federico II, Università di Napoli Federico II, via D. Montesano 49, 80131, Napoli, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mangoni
authors.affiliation: Institut für Mikrobiologie, Eidgenössiche Technische Hochschule (ETH) Zürich, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland.
authors.forename: Brandon I
authors.initials: BI
authors.lastname: Morinaka
authors.affiliation: Institut Pasteur, Collection des Cyanobactéries, Département de Microbiologie, 75015, Paris, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Gugger
authors.affiliation: Institut für Mikrobiologie, Eidgenössiche Technische Hochschule (ETH) Zürich, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland.
authors.forename: Jörn
authors.identifier: 0000-0002-2282-8154
authors.initials: J
authors.lastname: Piel
keywords: biosynthesis; meroterpenoid; natural products; structure elucidation; terpenoids