Genome-Driven Discovery of Neuraminidase-Inhibiting and Antibacterial Chermsinols A and B: Orsellinic-Acid-Derived Steroid and Meroterpenoid from Marine-Sourced <i>Penicillium chermesinum</i>

Two orsellinic acid (OA)-derived metabolites, chermsinols A and B ( 1 and 2 ), were isolated from the marine red alga-derived endophytic Penicillium chermesinum EN-480 based on its genomic analysis. Compound 1 is a steroid featuring an unprecedented 6/6/6/5/6/6 ring system, likely formed from a Diels–Alder reaction, while compound 2 is a meroterpenoid containing a unique ring-opened ketone chain derived from 3,5-dimethylorsellinic acid (DMOA) and possessing a continuous spiro system. Results from bioassays revealed that compound 1 exhibits inhibitory activity against influenza neuraminidase as well as antibacterial properties. The plausible biosynthetic pathways for 1 and 2 were proposed on the basis of the genomic data analysis of the producing fungus.