title: Identification of ten KB425796-A congeners from Paenibacillus sp. 530603 using an antifungal assay against Aspergillus fumigatus in combination with micafungin.
abstract: The discovery and characterization of natural congeners is one approach for understanding the relationship between chemical structure and biological function. We recently isolated the novel antifungal metabolite KB425796-A produced by the recently isolated bacterium Paenibacillus sp. 530603. On the basis of morphological changes of Aspergillus fumigatus induced by KB425796-A in combination with micafungin, we developed a highly sensitive screening method for the specific detection of KB425796-A congeners. Using this method, we isolated ten congeners of KB425796-A, named KB425796-B, -C, -D, -E, -F, -G, -H, -I, -J and -K, which exhibited diverse antifungal potencies against A. fumigatus. One of the most potent congeners, KB425796-C, had antifungal activities against several micafungin-resistant infectious fungi. KB425796-C can be a potential drug candidate for treating micafungin-resistant fungal infections.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan. hirohito.kai@astellas.com
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kai
authors.forename: Midori
authors.initials: M
authors.lastname: Yamashita
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Takase
authors.forename: Michizane
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Ikuko
authors.initials: I
authors.lastname: Nakamura
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kanasaki
authors.forename: Masami
authors.initials: M
authors.lastname: Ezaki
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nitta
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.forename: Noriaki
authors.initials: N
authors.lastname: Inamura
authors.forename: Akihiko
authors.initials: A
authors.lastname: Fujie
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D025141:Drug Resistance, Fungal; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000494:pharmacology*; D055666:Lipopeptides / Q000494:pharmacology*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D056507:Paenibacillus / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D047630:Depsipeptides; D054714:Echinocandins; C584028:KB425796-A; D055666:Lipopeptides; D000077551:Micafungin