Identification of a molecular target of a novel fungal metabolite, pyrrolizilactone, by phenotypic profiling systems

Yushi Futamura, Makoto Kawatani, Makoto Muroi, Harumi Aono, Toshihiko Nogawa, Hiroyuki Osada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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. A novel trypsin-like proteasome inhibitor: Pyrrolizilactone, a novel fungal metabolite, was identified from our microbial metabolite fraction library. With the aid of two phenotype profiling systems - MorphoBase and ChemProteoBase - we established that pyrrolizilactone is a unique proteasome inhibitor targeting trypsin-like activity of the proteasome.

Original languageEnglish
Pages (from-to)2456-2463
Number of pages8
JournalChemBioChem
Volume14
Issue number18
DOIs
Publication statusPublished - 2013 Dec
Externally publishedYes

Keywords

  • ChemProteoBase
  • MorphoBase
  • cancer
  • natural products
  • pyrrolizilactone

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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