title: Distribution of the antifungal agents sordarins across filamentous fungi.
abstract: Sordarins are a class of natural antifungal agents which act by specifically inhibiting fungal protein synthesis through their interaction with the elongation factor 2, EF2. A number of natural sordarins produced by diverse fungi of different classes have been reported in the literature. We have run an exhaustive search of sordarin-producing fungi using two different approaches consecutively, the first one being a differential sensitivity screen using a sordarin-resistant mutant yeast strain run in parallel with a wild type strain, and the second one an empiric screen against Candida albicans followed by early detection of sordarins by LC-MS analysis. Using these two strategies we have detected as many as 22 new strains producing a number of different sordarin analogues, either known (sordarin, xylarin, zofimarin) or novel (isozofimarin and 4'-O-demethyl sordarin). Sordarin and xylarin were the most frequently found compounds in the class. The producing strains were subjected to sequencing of the ITS region to determine their phylogenetic affinities. All the strains were shown to belong to the Xylariales, being distributed across three families in this order, the Xylariaceae, the Amphisphaeriaceae, and the Diatrypaceae. Despite being screened in large numbers, we did not find sordarin production in any other fungal group, including those orders where sordarin producing fungi are known to exist (i.e., Sordariales, Eurotiales, and Microascales), suggesting that the production of sordarin is a trait more frequently associated to members of the Xylariales than to any other fungal order.
authors.affiliation: Centro de Investigación Básica, Merck Sharp and Dohme de España, Josefa Valcarcel, 38, 28027 Madrid, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Vicente
authors.forename: Angela
authors.initials: A
authors.lastname: Basilio
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Platas
authors.forename: Javier
authors.initials: J
authors.lastname: Collado
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Bills
authors.forename: Antonio
authors.initials: A
authors.lastname: González del Val
authors.forename: Jesús
authors.initials: J
authors.lastname: Martín
authors.forename: José R
authors.initials: JR
authors.lastname: Tormo
authors.forename: Guy H
authors.initials: GH
authors.lastname: Harris
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Zink
authors.forename: Michael
authors.initials: M
authors.lastname: Justice
authors.forename: Jennifer Nielsen
authors.initials: JN
authors.lastname: Kahn
authors.forename: Fernando
authors.initials: F
authors.lastname: Peláez
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D002176:Candida albicans / Q000187:drug effects; D005658:Fungi / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D007192:Indenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010802:Phylogeny
chemical_list: D000935:Antifungal Agents; D007192:Indenes; C003329:sordarin