Identification of a Molecular Target of a Novel Fungal Metabolite,Pyrrolizilactone, by Phenotypic Profiling Systems |
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Authors: | Dr Yushi Futamura Dr Makoto Kawatani Dr Makoto Muroi Harumi Aono Dr Toshihiko Nogawa Prof Dr Hiroyuki Osada |
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Affiliation: | 1. Antibiotics Laboratory, RIKEN, 2‐1 Hirosawa, Wako, Saitama 351‐0198 (Japan);2. Chemical Biology Research Group, RIKEN CSRS, 2‐1 Hirosawa, Wako, Saitama 351‐0198 (Japan) |
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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. |
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Keywords: | cancer ChemProteoBase MorphoBase natural products pyrrolizilactone |
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