# New Cyclopeptides and Curvularins from Marine-Derived Fungal-Bacterial Symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532

## TL;DR

Scientists discovered new compounds from a marine fungal-bacterial symbiont that show potential against fungi and tuberculosis.

## Contribution

Identification of new cyclopeptides and curvularins with antimicrobial and anticancer properties from a marine-derived symbiont.

## Key findings

- Three new cyclic tetrapeptides and two new curvularin analogs were isolated from a marine symbiont.
- Compounds 7 and 8 showed significant activity against Mycobacterium tuberculosis and moderate cytotoxicity against cancer cells.
- Genomic analysis revealed 79 unique biosynthetic gene clusters in the fungal host.

## Abstract

Three new cyclic tetrapeptides (nectriatidels A-C, 1–3), two new curvularin analogs (6 and 7), and four known compounds (4 and 5, 8 and 9) were isolated from the marine-derived fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532, which was obtained from Mauritia arabica 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 1–5 showed moderate amphotericin B (AmB)-potentiating activity against Candida albicans. Compounds 7 and 8 exhibited significant activities against Mycobacterium tuberculosis, with MIC values of 32 and 16 μg/mL, respectively. Additionally, compounds 7 and 8 exhibited moderate cytotoxicity against human colorectal cancer cell lines DLD-1 and SW480, with IC50 values of 25~36 μM. Whole-genome sequencing of A. spelaeus 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.