Reaping the\nChemical Diversity of <i>Morinagamyces\nvermicularis</i> Using Feature-Based Molecular Networking

Moringadepsin (<b>6</b>) and\nchaetone B (<b>7</b>)\nwere isolated by us in the course of a conventional chemical screening\nof <i>Morinagamyces vermicularis</i> CBS 303.81, a fungus\nbelonging to the relatively underexplored family Schizotheciaceae\nof the phylum Ascomycota. Since these metabolites did not account\nfor the antifungal activity observed in a crude extract of this fungus,\nwe utilized an MS/MS-based molecular networking approach to get a\nthorough insight into the secondary metabolites produced by this strain.\nManual annotation of high-resolution fragmentation mass spectra by\nCANOPUS classified a major molecular family as putatively new thiodiketopiperazines.\nHowever, these results were opposite to the results of ChemWalker\nanalysis based solely on MS/MS data, assigning these metabolites as\nvarious polyketides. Thus, targeted preparative HPLC isolation focusing\non the most abundant features within this major molecular family resulted\nin the isolation of five secondary metabolites. Their structures were\nelucidated based on HRMS and NMR data as four new thiodiketopiperazine\nderivatives, botryosulfuranols D–G (<b>1</b>–<b>4</b>), alongside the known botryosulfuranol A (<b>5</b>). Compounds <b>1</b>–<b>3</b> and <b>5</b> exhibited moderate to weak antifungal activity against different\ntest strains, accounting for the initial antifungal activity observed\nfor its crude extract. Our study stressed the importance of full NMR-based\nstructure elucidation for metabolomics research.