title: Isolation, structure and biological activity of phomafungin, a cyclic lipodepsipeptide from a widespread tropical Phoma sp.
abstract: We isolated a cyclic lipodepsipeptide, phomafungin, from a Phoma sp. The distinct antifungal activity of phomafungin in the crude extract was initially discovered by mechanistic profiling in the Candida albicans fitness test. The purified compound contains a 28 member ring consisting of eight amino acids and a beta-hydroxy-gamma-methyl-hexadecanoic acid, and displays a broad spectrum of antifungal activity against Candida spp., Aspergillus fumigatus and Trichophyton mentagrophytes with MIC of 2-8 microg/ml, and toxicity to mice at 25 mg/kg. The linear peptide derived from opening of the lactone ring was devoid of antifungal activity as well as toxicity. Phomafungin has been identified in a number of Phoma spp. collected from Africa and the Indian and Pacific Ocean islands.
authors.affiliation: Natural Products Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Kithsiri
authors.initials: K
authors.lastname: Herath
authors.forename: Guy
authors.initials: G
authors.lastname: Harris
authors.forename: Hiranthi
authors.initials: H
authors.lastname: Jayasuriya
authors.forename: Deborah
authors.initials: D
authors.lastname: Zink
authors.forename: Scott
authors.initials: S
authors.lastname: Smith
authors.forename: Francisca
authors.initials: F
authors.lastname: Vicente
authors.forename: Gerald
authors.initials: G
authors.lastname: Bills
authors.forename: Javier
authors.initials: J
authors.lastname: Collado
authors.forename: Antonio
authors.initials: A
authors.lastname: González
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: Jennifer Nielsen
authors.initials: JN
authors.lastname: Kahn
authors.forename: Stefan
authors.initials: S
authors.lastname: Galuska
authors.forename: Robert
authors.initials: R
authors.lastname: Giacobbe
authors.forename: George
authors.initials: G
authors.lastname: Abruzzo
authors.forename: Emily
authors.initials: E
authors.lastname: Hickey
authors.forename: Paul
authors.initials: P
authors.lastname: Liberator
authors.forename: Deming
authors.initials: D
authors.lastname: Xu
authors.forename: Terry
authors.initials: T
authors.lastname: Roemer
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D001232:Aspergillus fumigatus / Q000187:drug effects; D047630:Depsipeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D055666:Lipopeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D014249:Trichophyton / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D047630:Depsipeptides; D055666:Lipopeptides; C539861:phomafungin