New Cyclopeptides and Curvularins from Marine-Derived Fungal-Bacterial Symbiont GXIMD 04541/ GXIMD 04532.

Three new cyclic tetrapeptides (nectriatidels A-C, -), two new curvularin analogs ( and ), and four known compounds ( and , and ) were isolated from the marine-derived fungal-bacterial symbiont GXIMD 04541/ GXIMD 04532, which was obtained from in shallow coastal waters. Their structures were elucidated through NMR spectroscopy and HRESIMS, and their absolute configurations were determined by Marfey's method and quantum chemical calculations. Compounds - showed moderate amphotericin B (AmB)-potentiating activity against . Compounds and exhibited significant activities against , with MIC values of 32 and 16 μg/mL, respectively. Additionally, compounds and exhibited moderate cytotoxicity against human colorectal cancer cell lines DLD-1 and SW480, with IC values of 25~36 μM. Whole-genome sequencing of revealed a 35.91 Mb assembly encoding 106 biosynthetic gene clusters (BGCs). antiSMASH analysis revealed that 79 of these BGCs (74.5%) displayed no significant similarity to known pathways in the MIBiG database, which is dominated by hybrid clusters, terpene, T1PKS, NRPS, and NRPS-like types. Genomic analysis identified the putative biosynthetic gene clusters for these metabolites and confirmed the fungal host as the predominant producer.