New Polyketides from a Hydrothermal Vent Sediment Fungus Trichoderma sp. JWM29-10-1 and Their Antimicrobial Effects

Abstract

Marine fungi-derived secondary metabolites are still an important source for the discovery of potential antimicrobial agents. Here, five new polyketides (1, 2, and 6-8) and seven known compounds (3-5 and 9-12) were obtained from the culture of the marine-derived fungus Trichoderma sp. JWM29-10-1. Their structures were identified by extensive spectrographic data analyses, including 1D and 2D NMR, UV, IR, and HR-ESI-MS. Further, the absolute configurations of new compounds were determined by circular dichroism (CD) spectrum and alkali-hydrolysis in combination with the in situ dimolybdenum CD method. Subsequently, the antimicrobial effects of these isolated compounds were assessed by examining the minimal inhibition concentration (MIC) with the broth microdilution assay. Compounds 1 and 2 exhibited potent antimicrobial activity against Helicobacter pylori, including multidrug-resistant strains, with MIC range values of 2-8 µg/mL. Moreover, compound 1 showed significant inhibitory effects on the growth of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and vancomycin-resistant Enterococcus faecium, which greatly threaten human health. This study demonstrates that chromone derivatives 1-2, especially for 1, could be potential lead compounds for the development of new antimicrobial agents and provides insight for future medicinal chemistry research.

Keywords: Trichoderma sp. JWM29-10-1; antibacterial effect; antifungal effect; marine-derived fungus; polyketide.

Figure 1

The chemical structures of compounds 1–12.

Figure 2

The key ¹H-¹H COSY and HMBC correlations of compounds 1, 2, and 6–8.

Figure 3

Key NOESY correlations (A) and CD spectrum (B) of 2.

Figure 4

Key NOESY correlations of 6 (A), the hydrolytic products of 6-8, 6A-8A (B), and CD spectra of complexes of 6A-8A with Mo₂(OAc)₄ (C).

Figure 5

Growth of seven bacterial strains exposed to compounds 1 and 2 at various concentrations after 72 h for H. pylori strains and after 24 h for other bacterial strains. OD₆₀₀, optical density at 600 nm. (A), Growth of H. pylori G27. (B), Growth of H. pylori JIGC360. (C), Growth of S. aureus ATCC 25923. (D), Growth of S. aureus USA300. (E), Growth of E. faecium ATCC 19434. (F), Growth of E. faecium 36235. (G), Growth of E. faecalis ATCC 29212.