Identification of a Molecular Target of a Novel Fungal Metabolite, Pyrrolizilactone, by Phenotypic Profiling Systems. Issue 18 (25th October 2013)

• Record Type: Journal Article
• Authors: Futamura, Yushi; Kawatani, Makoto; Muroi, Makoto; Aono, Harumi; Nogawa, Toshihiko; Osada, Hiroyuki
• Is Part Of: Chembiochem. Volume 14:Issue 18(2013)
• Page Start: 2456
• Page End: 2463
• Publication Date: 2013-10-25
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201300499
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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.</p> </abstract>