title: A microbial model of mammalian metabolism: biotransformation of 4,5-dimethoxyl-canthin-6-one using Cunninghamella blakesleeana CGMCC 3.970.
abstract: 1. A filamentous fungus, Cunninghamella blakesleeana CGMCC 3.970, was applied as a microbial system to mimic mammalian metabolism of 4,5-dimethoxyl-canthin-6-one (1). Compound 1 belongs to canthin-6-one type alkaloids, which is a major bioactive constituent of a traditional Chinese medicine (the stems of Picrasma quassioides). 2. After 72 h of incubation in potato dextrose broth, 1 was metabolized to seven metabolites as follows: 4-methoxyl-5-hydroxyl-canthin-6-one (M1), 4-hydroxyl-5-methoxyl-canthin-6-one (M2), canthin-6-one (M3), canthin-6-one N-oxide (M4), 10-hydroxyl-4,5-dimethoxyl-canthin-6-one (M5), 1-methoxycarbonl-β-carboline (M6), and 4-methoxyl-5-O-β-D-glucopyranosyl-canthin-6-one (M7). 3. The structures of metabolites were determined using spectroscopic analyses, chemical methods, and comparison of NMR data with those of known compounds. Among them, M7 was a new compound. 4. The metabolic pathways of 1 were proposed, and the metabolic processes involved phase I (O-demethylation, dehydroxylation, demethoxylation, N-oxidation, hydroxylation, and oxidative ring cleavage) and phase II (glycosylation) reactions. 5. This was the first research on microbial transformation of canthin-6-one alkaloid, which could be a useful microbial model for producing the mammalian phase I and phase II metabolites of canthin-6-one alkaloids. 6. 1, M1-M5, and M7 are canthin-6-one alkaloids, whereas M6 belongs to β-carboline type alkaloids. The strain of Cunninghamella blakesleeana can supply an approach to transform canthin-6-one type alkaloids into β-carboline type alkaloids.
authors.affiliation: a Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University , Guangzhou , P.R. China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Fan
authors.affiliation: a Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University , Guangzhou , P.R. China.
authors.forename: Zheng-Qun
authors.initials: ZQ
authors.lastname: Zhou
authors.affiliation: c College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University , Shenyang , P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.affiliation: b Division of Pharmaceutics , College of Pharmacy, Jinan University , Guangzhou , P.R. China , and.
authors.forename: Bao-Jian
authors.initials: BJ
authors.lastname: Wu
authors.affiliation: a Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University , Guangzhou , P.R. China.
authors.forename: He-Ru
authors.initials: HR
authors.lastname: Chen
authors.affiliation: a Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University , Guangzhou , P.R. China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Bao
authors.affiliation: c College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University , Shenyang , P.R. China.
authors.forename: Zhen-Qiang
authors.initials: ZQ
authors.lastname: Mu
authors.affiliation: c College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University , Shenyang , P.R. China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jiao
authors.affiliation: a Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University , Guangzhou , P.R. China.|c College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University , Shenyang , P.R. China.
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Yao
authors.affiliation: a Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University , Guangzhou , P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Gao
mesh_terms: D001711:Biotransformation; D002243:Carbolines / Q000378:metabolism*; D020093:Cunninghamella / Q000378:metabolism*; D026121:Indole Alkaloids / Q000378:metabolism*
chemical_list: D002243:Carbolines; D026121:Indole Alkaloids; C453379:canthin-6-one
keywords: 4,5-Dimethoxyl-canthin-6-one; Cunninghamella blakesleeana; canthin-6-one alkaloids; microbial model of mammalian metabolism; microbial transformation