Genome Mining of a Prenylated and Immunosuppressive Polyketide from Pathogenic Fungi

Abstract

Activation of the polycyclic polyketide prenyltransferase (pcPTase)-containing silent clusters in <i>Aspergillus fumigatus</i> and <i>Neosartorya fischeri</i> led to isolation of a new metabolite neosartoricin (<b>3</b>). The structure of <b>3</b> was solved by X-ray crystallography and NMR to be a prenylated anthracenone. <b>3</b> exhibits T-cell antiproliferative activity with an IC₅₀ of 3 μM, suggestive of a physiological role as an immunosuppressive agent