Polyketide Production of Pestaloficiols and Macrodiolide Ficiolides Revealed by Manipulations of Epigenetic Regulators in an Endophytic Fungus

Regarding targeted disruption of epigenetic regulators, histone methyltransferase and deacetylase in a plant endophytic fungus Pestalotiopsis fici have been uncovered as an unexplored chemical repertoire. Manipulation of epigenetic regulators led to the isolation of 15 new polyketides, including pestaloficiols T–W (1–3 and 5), as well as 11 macrodiolide ficiolides A–K (6–16). Ficiolide K (16) was found to contain a very rare 1,6-anhydro-pyranose moiety. Finally, the biosynthetic origin of macrodiolide was characterized by isotope-labeling experiments.