Modulating Activity Evaluation of Gut Microbiota with Toluquinol from Penicillium Colonization. Modulating Activity Evaluation of Gut Microbiota with Toluquinol from Penicillium Colonization

Increasing evidences suggested that gut microbiota has important implications for health by affecting metabolism of dietary and drugs. However, the mediators and their mechanisms in modulating metabolites from fungal origins remain largely unknown. Toluquinol as a key versatile precursor metabolite has been commonly distributed in Penicillium species including the strains for food production. Comparing metabolite profile differences from 17 common gut microbes fed with toluquinol or vehicle, we identified that four strains, belonging to predominant Enterococcus species, could metabolize toluquinol and produce different metabolites. Chemical investigation on large scale cultures led to isolation of four targeted metabolites and their structures were characterized with NMR, MS and X-ray diffraction analysis, as four toluquinol derivatives (1-4) through O1/O4-acetyl and C5/C6-methylsulfonyl substitutions, respectively. All the four metabolites were first synthesized in living organisms. Further experiment suggested that the rare methylsulfonyl groups in 3-4 were donated from solvent DMSO through Fenton’s reaction. Metabolite 1 displayed the strongest inhibitory effect on cancer cells A549, A2780 and G401 with IC50 values at 0.224, 0.204 and 0.597 μM, while metabolite 3 displayed no effect. Our results suggested that the dominant Enterococcus species should modulate potential precursors and their biological activity.