AMIDEPSINES, INHIBITORS OF DIACYLGLYCEROL ACYLTRANSFERASE PRODUCED BYHUMICOLA SP FO-2942 .1. PRODUCTION, ISOLATION AND BIOLOGICAL PROPERTIES

Humicola sp. FO-2942, a soil isolate, was found to produce a series of new inhibitors of diacylglycerol acyltransferase (DGAT). Three active compounds, designated amidepsines A, B and C, were isolated from the fermentation broth of the producing strain by solvent extraction, sili ca gel column chromatography, ODS column chromatography and HPLC. Amid epsines inhibit DGAT activity with IC50 values of 10.2 similar to 51.6 mu M in an enzyme assay system using rat liver microsomes. Amidepsine s also showed specific inhibition of triacylglycerol formation in inta ct Raji cells, indicating that they inhibit DGAT activity in living ce lls.