title: Demethylation of Polymethoxyflavones by Human Gut Bacterium, Blautia sp. MRG-PMF1.
abstract: Polymethoxyflavones (PMFs) were biotransformed to various demethylated metabolites in the human intestine by the PMF-metabolizing bacterium, Blautia sp. MRG-PMF1. Because the newly formed metabolites can have different biological activities, the pathways and regioselectivity of PMF bioconversion were investigated. Using an anaerobic in vitro study, 12 PMFs, 5,7-dimethoxyflavone (5,7-DMF), 5-hydroxy-7-methoxyflavone (5-OH-7-MF), 3,5,7-trimethoxyflavone (3,5,7-TMF), 5-hydroxy-3,7-dimethoxyflavone (5-OH-3,7-DMF), 5,7,4'-trimethoxyflavone (5,7,4'-TMF), 5-hydroxy-7,4'-dimethoxyflavone (5-OH-7,4'-DMF), 3,5,7,4'-tetramethoxyflavone (3,5,7,4'-TMF), 5-hydroxy-3,7,4'-trimethoxyflavone (5-OH-3,7,4'-TMF), 5,7,3',4'-tetramethoxyflavone (5,7,3',4'-TMF), 3,5,7,3',4'-pentamethoxyflavone (3,5,7,3',4'-PMF), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (5-OH-3,7,3',4'-TMF), and 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (5,3'-diOH-3,7,4'-TMF), were converted to chrysin, apigenin, galangin, kaempferol, luteolin, and quercetin after complete demethylation. The time-course monitoring of PMF biotransformations elucidated bioconversion pathways, including the identification of metabolic intermediates. As a robust flavonoid demethylase, regioselectivity of PMF demethylation generally followed the order C-7 > C-4' ≈ C-3' > C-5 > C-3. PMF demethylase in the MRG-PMF1 strain was suggested as a Co-corrinoid methyltransferase system, and this was supported by the experiments utilizing other methyl aryl ether substrates and inhibitors.
authors.affiliation: Metalloenzyme Research Group and Department of Integrative Plant Science, Chung-Ang University , Anseong 17546, Korea.
authors.forename: Supawadee
authors.initials: S
authors.lastname: Burapan
authors.affiliation: Metalloenzyme Research Group and Department of Integrative Plant Science, Chung-Ang University , Anseong 17546, Korea.
authors.forename: Mihyang
authors.initials: M
authors.lastname: Kim
authors.affiliation: Metalloenzyme Research Group and Department of Integrative Plant Science, Chung-Ang University , Anseong 17546, Korea.
authors.forename: Jaehong
authors.identifier: http://orcid.org/0000-0002-5328-3927
authors.initials: J
authors.lastname: Han
mesh_terms: D001711:Biotransformation; D000068536:Bacillota / Q000302:isolation & purification / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008745:Methylation
chemical_list: D005419:Flavonoids
keywords: Blautia; Co-corrinoid; biotransformation; flavonoid; human intestinal bacteria; polymethoxyflavone; regioselectivity