"Discovery of useful bioactive compounds from microorganisms", Prof Hiroshi TOMODA

Abstract:
Our research group has focused on the discovery of new bioactive compounds from microorganisms. Particularly, I have been interested in inhabitors of lipid metabolism which is closely linked to various diseases.
In the seminar, our experience about fungal pyripyropene A study will be presented.

Story about pyripyropene A (PPPA)

1. PPPA was originally isolated as a potent inhibitor of acyl-CoA:cholesterol  acyltransferase (ACAT) from a culture broth of Aspergillus fumigatus FO-1289.
2. Two ACAT isozymes, ACAT1 and ACAT2, were identified and have a distinct function in mammals. PPPA was found to be the first ACAT2-selective inhibitor.
3. PPPA proved orally active in atherogenic mouse models.
4. PPPA derivatives with more potent and more ACAT2-selective inhibitory activity were discovered.They showed more effective than PPPA in the mouse models. We believe the PPPA derivatives are promising as a post-statin drug.