Demethylation of Polymethoxyflavones by Human Gut Bacterium, Blautia sp. MRG-PMF1

Area of Science:

• Microbiology and Biochemistry
• Natural Product Metabolism
• Human Gut Microbiome

Background:

• Polymethoxyflavones (PMFs) are plant-derived compounds with potential biological activities.
• The human gut microbiome plays a crucial role in metabolizing dietary compounds, influencing their bioavailability and efficacy.
• Biotransformation of PMFs by gut bacteria can yield metabolites with altered biological properties.

Purpose of the Study:

• To investigate the biotransformation pathways and regioselectivity of 12 different PMFs by Blautia sp. MRG-PMF1.
• To identify intermediate metabolites formed during PMF demethylation.
• To elucidate the enzymatic mechanism of PMF demethylation.

Main Methods:

• Anaerobic in vitro incubation of 12 selected PMFs with Blautia sp. MRG-PMF1.
• Time-course monitoring of PMF bioconversion to identify metabolic intermediates and pathways.
• Analysis of regioselectivity of demethylation using various PMF substrates and inhibitors.
• Experiments with other methyl aryl ether substrates to support the proposed enzymatic system.

Main Results:

• Blautia sp. MRG-PMF1 completely demethylated 12 PMFs into chrysin, apigenin, galangin, kaempferol, luteolin, and quercetin.
• Bioconversion pathways and key metabolic intermediates were identified through time-course monitoring.
• The regioselectivity of PMF demethylation followed a consistent order: C-7 > C-4' ≈ C-3' > C-5 > C-3.
• The PMF demethylase activity was suggested to be a Co-corrinoid methyltransferase system.

Conclusions:

• Blautia sp. MRG-PMF1 possesses a robust PMF demethylase capable of extensive demethylation of various PMFs.
• The study elucidated the specific pathways and regioselectivity of PMF biotransformation in the human gut.
• The findings suggest a Co-corrinoid methyltransferase system is responsible for PMF demethylation by this bacterium.