# Polydosetins & pullularins—bioactive tetramic acids & cyclodepsipeptides from the endophytic and nematophagous fungus Polydomus karssenii

## TL;DR

Scientists discovered seven new bioactive compounds from a fungus linked to nematodes, showing potential antimicrobial and nematicidal properties.

## Contribution

The discovery of seven new natural products from Polydomus karssenii, including their structural elucidation and bioactivity assessment.

## Key findings

- Polydosetins A–E and pullularins G and H were isolated and structurally characterized.
- Some compounds showed activity against Gram-positive bacteria, fungi, and nematodes.
- The study highlights the potential of nematode-associated fungi as sources of new bioactive compounds.

## Abstract

In course of investigating the endophytic and nematode-associated fungus Polydomus karssenii for the production of secondary metabolites, seven previously undescribed natural products were isolated from liquid and solid-state fermentations. 1D and 2D NMR spectroscopy, together with HR-ESI–MS data, enabled the elucidation of the planar structures of 3-decalinoyltetramic acids polydosetins A–E (1–5) and cyclodepsipeptides pullularins G and H (6 and 7). The relative configurations of the decalin moiety of 1–5 were determined based on ROESY correlations and 1H–1H coupling constants. The configuration of the side chains was established through a detailed J-resolved analysis (Murata’s method) in combination with chemical shift comparison to model compounds. Absolute stereochemistry of 1–5 was assigned based on ECD data, and confirmed by Mosher’s method utilizing 3. Finally, the absolute configuration of amino acid residues in 6 and 7 was determined through advanced Marfey’s method. Bioassays revealed that compounds 1, 3, 5, and 7 were active against Gram-positive bacteria, 3 and 5 exhibited antifungal activity, and 1 and 2 showed nematicidal effects. These results underscore the untapped chemical potential of P. karssenii and highlight the importance of exploring nematode-associated fungi as sources of new natural products with potential antimicrobial and nematicidal properties.

The online version contains supplementary material available at 10.1007/s13659-025-00579-8.