Bioprospection of Tenellins Produced by the Entomopathogenic Fungus Beauveria neobassiana

Abstract

Fungi are known as prolific producers of bioactive secondary metabolites with applications across various fields, including infectious diseases, as well as in biological control. However, some of the well-known species are still underexplored. Our current study evaluated the production of secondary metabolites by the entomopathogenic fungus Beauveria neobassiana from Thailand. The fermentation of this fungus in a liquid medium, followed by preparative high-performance liquid chromatography (HPLC) purification, resulted in the isolation of a new tenellin congener, namely pretenellin C (1), together with five known derivatives (2-6). Their chemical structures were elucidated by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy in combination with high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). We evaluated the antimicrobial and cytotoxic activities from all isolated compounds, as well as their inhibitory properties on biofilm formation by Staphylococcus aureus. Generally, tenellins displayed varying antibiofilm and cytotoxic effects, allowing us to propose preliminary structure-activity relationships (SARs). Among the tested compounds, prototenellin D (2) exhibited the most prominent antibiofilm activity, while its 2-pyridone congener, tenellin (4), demonstrated potent cytotoxic activity against all tested cell lines. Given the fact that the biological activities of the tenellins have so far been neglected in the past, our study could provide a good starting point to establish more concise structure-activity relationships in the near future.

Keywords: Cordycipitaceae; PKS-NRPS; SAR; antiproliferative; biofilm inhibition; insect fungi.

Figure 1

(A) HPLC−UV/Vis chromatograms (210 nm) of the crude extracts obtained from the mycelia and supernatant from the scaled-up fermentation of B. neobassiana in PDB medium. (B) Chemical structures of the isolated metabolites 1–6.

Figure 2

Key ¹H-¹H COSY and HMBC correlations of 1.

Figure 3

Inhibitory activity of compounds 1–6 and microporenic acid (MAA, positive control) on biofilm formation of S. aureus compared to the solvent control (MeOH, 0% biofilm inhibition). Error bars indicate SD of triplicates; p values: ** p < 0.01, *** p < 0.001. Differences between samples and the control group were determined by a two-tailed Student’s t-test. Statistical significance was defined as p < 0.01.