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

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.