Filamentous fungi are abundant resources of bioactive natural products. Here, 151 marine-derived fungi were collected from the north Yellow Sea and identified by an internal transcribed spacer (ITS) sequence. The crude extracts of all strains were evaluated for their antimicrobial activities and analyzed by HPLC fingerprint. Based on these, strain Penicillium oxalicum MEFC104 was selected for further investigation. Two new polyketide-amino acid hybrid compounds with feature structures of tetramic acid, oxopyrrolidine A and B, were isolated. Their planner structures were assigned by HRESIMS and 1D/2D NMR experiments. The absolute configurations were determined by modified Mosher's method, J-based configuration analysis, and ECD calculations. Furthermore, the biosynthetic pathway was identified by bioinformatic analysis and gene-deletion experiments. This study established a link between oxopyrrolidines and the corresponding biosynthesis genes in P. oxalicum.
Keywords: biosynthesis; gene cluster; marine-derived fungi; oxopyrrolidines.