title: Identification of a molecular target of a novel fungal metabolite, pyrrolizilactone, by phenotypic profiling systems.
abstract: In the course of screening our microbial metabolite fraction library, we identified a novel pyrrolizidinone compound, pyrrolizilactone. In this study, we report the identification and characterization of a molecular target for pyrrolizilactone by using two phenotypic profiling systems. Cell morphology-based profiling analysis using an imaging cytometer (MorphoBase) classified pyrrolizilactone as a proteasome inhibitor. Consistently, proteome-based profiling analysis using 2D difference gel electrophoresis (DIGE; ChemProteoBase) also demonstrated that pyrrolizilactone is associated with proteasome inhibition. On the basis of these predictions, we determined that pyrrolizilactone is a novel type of proteasome inhibitor inhibiting the trypsin-like activity of the proteasome.
authors.affiliation: Antibiotics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan).
authors.forename: Yushi
authors.initials: Y
authors.lastname: Futamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawatani
authors.forename: Makoto
authors.initials: M
authors.lastname: Muroi
authors.forename: Harumi
authors.initials: H
authors.lastname: Aono
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nogawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D016208:Databases, Factual; D005658:Fungi / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D061988:Proteasome Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D007783:Lactones; D061988:Proteasome Inhibitors
keywords: ChemProteoBase; MorphoBase; cancer; natural products; pyrrolizilactone