title: Isolation, structure elucidation and biological activity of metabolites from Sch-642305-producing endophytic fungus Phomopsis sp. CMU-LMA.
abstract: Eight polyketide compounds were isolated from the cultivation broth of Phomopsis sp. CMU-LMA. We have recently described LMA-P1, a bicyclic 10-membered macrolide, obtained as a bioconversion derivative of Sch-642305, the major compound isolated in this study. Benquinol is the ethyl ester derivative of the 13-dihydroxytetradeca-2,4,8-trienoic acid produced by Valsa ambiens. This compound is concomitantly produced with the 6,13-dihydroxytetradeca-2,4,8-trienoic acid (DHTTA) previously isolated from Mycosphaerellarubella. The absolute configuration of the new compound, (2R,3R,4S,5R)-3-hydroxy-2,4-dimethyl-5-[(S,Z)-3-methylpentenyl]-tetrahydro-pyranone LMA-P2 was confirmed by X-ray crystallography. The δ-lactone 2,3-dihydroxytetradecan-5-olide (DHTO) was previously isolated from Seiridium unicorne. This compound may form through the cyclization of the methyl-2,3,5-trihydroxytridecanoate LMA-P3, a new linear polyketide isolated in this study. Benquoine, a new 14-membered lactone generated from the cyclization of benquinol, is proposed as the key precursor for the biosynthesis of Sch-642305. Antimicrobial activity and cancer cell viability inhibition by the new compounds were investigated. Benquoine exhibits antimicrobial activity against Gram positive bacteria, and cytotoxicity against HCT-116 cancer cell line.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles ICSN, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Adelin
authors.forename: Claudine
authors.initials: C
authors.lastname: Servy
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cortial
authors.forename: Hélène
authors.initials: H
authors.lastname: Lévaique
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Martin
authors.forename: Pascal
authors.initials: P
authors.lastname: Retailleau
authors.forename: Géraldine
authors.initials: G
authors.lastname: Le Goff
authors.forename: Boonsom
authors.initials: B
authors.lastname: Bussaban
authors.forename: Saisamorn
authors.initials: S
authors.lastname: Lumyong
authors.forename: Jamal
authors.initials: J
authors.lastname: Ouazzani
mesh_terms: D000818:Animals; D001203:Ascomycota / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000187:drug effects; D018942:Macrolides / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D019906:Nuclear Magnetic Resonance, Biomolecular; D061065:Polyketides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D018942:Macrolides; D061065:Polyketides; C482741:Sch 642305