Novel Metabolites of Xylaria thienhirunae SWUF17-44.1 with Biological Activities and Molecular Docking Analysis

TL;DR

A new fungus produces bioactive compounds with strong antibacterial and antioxidant properties, especially against Gram-positive bacteria.

Contribution

Discovery of two novel metabolites with potent antimicrobial activity and strong in silico interactions with bacterial targets.

Findings

Extract showed strong antimicrobial activity against Gram-positive bacteria with MICs as low as 0.63 µg/µL.

Two novel compounds, xylerithienol and xylerithiether, exhibited antibacterial activity and strong in silico docking with bacterial targets.

Xylerithiether outperformed norfloxacin and fluconazole in inhibiting specific bacterial enzymes.

Abstract

The extract of Xylaria thienhirunae SWUF17-44.1 displayed broad-spectrum antimicrobial activity, with higher potency against Gram-positive bacteria than Gram-negative strains. Minimum inhibitory concentration (MIC) values were as low as 0.63 µg/µL for Staphylococcus aureus and 1.25 µg/µL for Bacillus subtilis, whereas higher values were observed for Escherichia coli and Pseudomonas aeruginosa. The extract also inhibited fungal growth, with MICs of 6.25 μg/μL against Candida albicans and C. tropicalis. Strong antioxidant activity was observed (DPPH IC50 = 0.706 ± 0.022 μg/μL; ABTS IC50 = 0.251 ± 0.019 μg/μL), correlated with high phenolic content. Moderate anti-inflammatory activity was confirmed via nitric oxide inhibition. LC-MS profiling indicated diverse metabolites, including phenolic derivatives, aminoglycoside-like compounds, and annotated bioactive molecules. Chromatographic isolation yielded four compounds: 4-(2,3-dihydroxypropoxy)benzoic acid, 4-prenyloxybenzoic acid, and two novel metabolites, xylerithienol and xylerithiether. In silico docking predicted strong interactions of the novel compounds with bacterial targets such as muramyl ligases, DNA gyrase B, and β-ketoacyl-ACP synthase III. Notably, xylerithiether outperformed norfloxacin against DNA gyrase B and fluconazole against sterol 14-α-demethylase. In vitro antibacterial activity was assessed for the purified compounds; all were active, predominantly against Gram-positive bacteria. These finding position X. thienhirunae SWUF17-44.1 as a promising source of bioactive metabolites and potential scaffolds for antimicrobial drug discovery.

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