title: Manipulation of heterogeneity product in 4'-demethylepipodophyllotoxin biotransformation process by using yeast extract as nitrogen source.
abstract: Manipulation of product heterogeneity was attempted by using yeast extract as nitrogen source in Alternaria alternata S-f6 transformation process of 4'-demethylepipodophyllotoxin. When the nitrogen source of NaNO(3) was replaced by yeast extract, the heterogeneity of biotransformation products was significantly varied from a single product (i.e., 4'-demethylpodophyllotoxone) to four podophyllum derivates. According to the kinetics of 4'-demethylepipodophyllotoxin biotransformation process by A. alternata S-f6, the starting substrate of 4'-demethylepipodophyllotoxin was preferentially transformed to produce 4'-demethylpodophyllotoxone (1) with an oxidation reaction. By the further comparison of products configuration, 4β-caprinoyl-4'-demethylepipodophyllotoxin (3) was produced from 4'-demethylpodophyllotoxone (1) instead of 4'-demethylisopicropodophyllone (2), which might be produced from 4'-demethylpodophyllotoxone (1) with the isomerization of lactone. Finally, 4'-demethylisopicropodophyllone (2) was hydrolyzed to produce 3α-hydroxymethyl-(6, 7)-dioxol-4-one-naphthalene (4). This work shows new information on the 4'-demethylepipodophyllotoxin biotransformation process by A. alternata S-f6 and provides a foundation for further studies on the structural diversification of a bioactive natural lead compound.
authors.affiliation: Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Key Laboratory of Industrial Microbiology, College of Bioengineering, Hubei University of Technology, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Li
authors.forename: Duan-Ji
authors.initials: DJ
authors.lastname: Wan
authors.forename: Ya-Jie
authors.initials: YJ
authors.lastname: Tang
mesh_terms: D000528:Alternaria / Q000254:growth & development / Q000378:metabolism*; D001711:Biotransformation; D003470:Culture Media / Q000737:chemistry*; D009584:Nitrogen / Q000378:metabolism*; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D003470:Culture Media; D011034:Podophyllotoxin; D009584:Nitrogen; C072088:4'-demethylepipodophyllotoxin