Genome Mining of a Deep-Sea-Derived <i>Penicillium allii-sativi</i> Revealed Polyketide-Terpenoid Hybrids with Antiosteoporosis Activity

Abstract

Two novel meroterpenoids, alliisativins A and B (<b>1</b>, <b>2</b>) were discovered through a genome-based exploration of the biosynthetic gene clusters of the deep-sea-derived fungus <i>Penicillium allii-sativi</i> MCCC entry 3A00580. Extensive spectroscopic analysis, quantum calculations, chemical derivatization, and biogenetic considerations were utilized to establish their structures. Alliisativins A and B (<b>1</b>, <b>2</b>) possess a unique carbon skeleton featuring a drimane sesquiterpene with a highly oxidized polyketide. Noteworthily, alliisativin A (<b>1</b>) showed dual activity in promoting osteogenesis and inhibiting osteoclast, indicating an antiosteoporosis potential.