Pyrrolizilactone

Structure
NPEdia
Producing organism
an uncharacterized fungus
Biological activity
proteasome inhibitor
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.
References
  • Nogawa T, Kawatani M, Uramoto M, Okano A, Aono H, Futamura Y, Koshino H, Takahashi S, Osada H.: Pyrrolizilactone, a new pyrrolizidinone metabolite produced by a fungus.
    J Antibiot, 66(10): 621-623 (2013) PMID: 23715039 [ doi: 10.1038/ja.2013.55 ]
  • Futamura Y, Kawatani M, Muroi M, Aono H, Nogawa T, Osada H.: Identification of a molecular target of a novel fungal metabolite, pyrrolizilactone, by phenotypic profiling systems.
    Chembiochem, 14(18): 2456-2463 (2013) PMID: 24166831 [ doi: 10.1002/cbic.201300499 ]
  • Additional information