Uncovering Biosynthetic Potential of Plant-associated Fungi: Effect of Culture Conditions on Metabolite Production by Paraphaeosphaeria Quadriseptata and Chaetomium Chiversii

In an attempt to uncover the biosynthetic potential of plant-associated fungi, the effect of culture conditions on metabolite production by Paraphaeosphaeria quadriseptata and Chaetomium chiversii was investigated. These studies indicated that the production of the major metabolites by P. quadriseptata differ when the water used to make the media was changed from tap water to distilled water. It resulted in the isolation of six new secondary metabolites, cytosporones F-I ( 1- 4), quadriseptin A ( 5), and 5'-hydroxymonocillin III ( 6) together with monocillin III ( 7), a metabolite new to P. quadriseptata, in addition to monocillin I ( 8), a previously known metabolite from this organism. Aposphaerin B ( 9) encountered was suspected to be an artifact originating from cytosporone F ( 1). Incorporation of heavy metal ions to P. quadriseptata culture medium induced production of monocillin I ( 8) by this fungus. Cultivation of C. chiversii in liquid medium resulted in the isolation of chaetochromin A ( 12) as the major metabolite instead of radicicol ( 10), the major constituent of this organism when grown in a solid medium. Compounds 1- 7 and 12 were evaluated for their potential to inhibit Hsp90 and antiproliferative activity toward the cancer cell lines NCI-H460, MCF-7, and SF-268. Only compounds 6, 7, and 8 exhibited significant activity in both assays.