Asperanstinoids A-E: Undescribed 3,5-dimethylorsellinic acid-based meroterpenoids from Aspergillus calidoustus

Large-scale culture is a complementary and practical method for genome mining and OSMAC approaches to discover novel natural products through accumulation and reprocessing effects. By employing a large-scale culture approach, twelve 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoids, including five undescribed compounds, namely asperanstinoids A-E, were obtained from fungus Aspergillus calidoustus, which was isolated from the wetland soil collected at Dianchi Lake, Yunnan Province. The structures and absolute configurations of asperanstinoids A-E were determined by various spectroscopic analyses, including NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations, and the absolute configurations of three known compounds, dehydroaustinol, austinol, and austin, were confirmed via single-crystal X-ray diffraction for the first time. Notably, asperanstinoid A represents the second example of a DMOA-based meroterpenoid featuring a unique 6/ 5/6/6/6/5-fused hexacyclic skeleton with a rare 1,13-epoxy moiety. The cytotoxicity assay of all these isolates revealed that asperanstinoid D, dehydroaustinol, and austin displayed considerable cytotoxicity against the HL60 and SU-DHL-4 tumor cell lines with IC50 values ranging from 15.7 to 27.8 mu M.

Automated summary

Large-scale culture was used to discover twelve new meroterpenoids from fungus Aspergillus calidoustus isolated from wetland soil in Yunnan Province, including five undescribed asperanstinoids. Asperanstinoid A, with a unique fused hexacyclic skeleton and rare epoxy moiety, showed significant cytotoxicity against tumor cell lines HL60 and SU-DHL-4.