title: 11-Hydroxylation of Protoberberine by the Novel Berberine-Utilizing Aerobic Bacterium Sphingobium sp. Strain BD3100.
abstract: Protoberberine alkaloids, including berberine, palmatine, and berberrubine, are produced by medicinal plants and are known to have various pharmacological effects. We isolated two berberine-utilizing bacteria, Sphingobium sp. strain BD3100 and Rhodococcus sp. strain BD7100, from soil collected at a natural medicine factory. BD3100 had the unique ability to utilize berberine or palmatine as the sole carbon and energy source. BD3100 produced demethyleneberberine in berberine-supplemented medium. In a resting-cell incubation with berberine, BD3100 produced 11-hydroxyberberine; the structure of 11-hydroxyberberine was determined by detailed analysis of NMR and MS spectroscopic data. α-Naphthoflavone, miconazole, and ketoconazole, which are known inhibitors of cytochrome P450, interfered with BD3100 metabolism of berberine in resting cells. Inhibition by miconazole led to the production of a new compound, 11-hydroxydemethyleneberberine. In a resting-cell incubation with palmatine, BD3100 generated 11-hydroxypalmatine. This work represents the first report of the isolation and characterization of novel berberine-utilizing aerobic bacteria for the production of 11-hydroxylation derivatives of berberine and palmatine.
authors.affiliation: Department of Organic Chemistry, Hoshi University , 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Department of Organic Chemistry, Hoshi University , 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Department of Organic Chemistry, Hoshi University , 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Wakana
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology , 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University , Kitashirakawa, Sakyo, Kyoto 606-8317, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Organic Chemistry, Hoshi University , 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Hosoe
mesh_terms: D001571:Benzoflavones / Q000737:chemistry; D001599:Berberine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D001600:Berberine Alkaloids / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006900:Hydroxylation; D007564:Japan; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry; D042301:Sphingomonadaceae / Q000235:genetics / Q000378:metabolism*
chemical_list: C549168:11-hydroxypalmatine; D001571:Benzoflavones; D001600:Berberine Alkaloids; D065607:Cytochrome P-450 Enzyme Inhibitors; D001599:Berberine; C115958:berberrubine; C009090:protoberberine; C477155:demethyleneberberine; C011512:alpha-naphthoflavone; C005413:palmatine