Modulating Activity Evaluation of Gut Microbiota with Versatile Toluquinol

Area of Science:

• Microbiology
• Mycology
• Metabolomics

Background:

• Gut microbiota influence host health by metabolizing dietary and xenobiotic compounds.
• Fungal metabolites, such as toluquinol, are present in the gut but their microbial transformation and biological activity remain poorly understood.

Purpose of the Study:

• To investigate the microbial metabolism of fungal-derived toluquinol by human gut bacteria.
• To identify and characterize the metabolites produced and assess their biological activities, particularly their effects on cancer cells.

Main Methods:

• Cultivation of 17 common gut microbes with and without toluquinol.
• Metabolic analysis to identify toluquinol-metabolizing strains.
• Chemical isolation and structural elucidation (NMR, MS, X-ray diffraction) of resulting metabolites.
• In vitro cancer cell line assays (A549, A2780, G401) to determine cytotoxicity.

Main Results:

• Four gut microbial strains, including Enterococcus species, metabolized toluquinol.
• Four toluquinol derivatives (1-4) were isolated and characterized, featuring acetyl and methylsulfonyl substitutions.
• Metabolites 3 and 4 incorporated methylsulfonyl groups from DMSO via Fenton's reaction.
• Metabolite 1 exhibited potent inhibition against A549, A2780, and G401 cancer cells (IC50 values 0.224-0.597 μM).

Conclusions:

• Dominant gut bacteria, particularly Enterococcus species, can significantly modify fungal precursor metabolites like toluquinol.
• Microbial transformation alters the biological activity of fungal metabolites, with derivative 1 showing strong anti-cancer properties.