Inducing Secondary Metabolite Production by Combined Culture of Talaromyces aculeatus and Penicillium variabile

Four new polyketides, penitalarins A–C (1–3) and nafuredin B (4), together with the known biogenetically related nafuredin A (5) were isolated from a mixed culture of a deep-sea-derived fungus Talaromyces aculeatus and a mangrove-derived fungus Penicillium variabile. Liquid chromatography/mass spectrometry analysis showed that none of compounds 1–5 was produced by either of the two fungi when cultured alone under the same condition. The structures of 1–4, including absolute configurations, were deduced based on the interpretation of MS, NMR data, and time-dependent density functional theory calculations of specific electronic circular dichroism spectra. Compounds 1–3 possess a 3,6-dioxabicyclo[3.1.0]hexane ring, and 4 showed cytotoxicity with IC50 values ranging from 1.2 to 9.8 μM against a panel of human cancer cell lines.