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Novel Tandem Biotransformation Process for the Biosynthesis of a Novel Compound, 4-(2,3,5,6-Tetramethylpyrazine-1)-4 '-Demethylepipodophyllotoxin
Tang, Ya-Jie1,2,3,4; Zhao, Wei1,2; Li, Hong-Mei1,2; Tang, YJ
2011-05-01
Source PublicationAPPLIED AND ENVIRONMENTAL MICROBIOLOGY
ISSN0099-2240
Volume77Issue:9Pages:3023-3034
AbstractAccording to the structure of podophyllotoxin and its structure-function relationship, a novel tandem biotransformation process was developed for the directional modification of the podophyllotoxin structure to directionally synthesize a novel compound, 4-(2,3,5,6-tetramethylpyrazine-1)-4'-demethylepipodophyllotoxin (4-TMP-DMEP). In this novel tandem biotransformation process, the starting substrate of podophyllotoxin was biotransformed into 4'-demethylepipodophyllotoxin (product 1) with the demethylation of the methoxyl group at the 4' position by Gibberella fujikuroi SH-f13, which was screened out from Shennongjia prime forest humus soil (Hubei, China). 4'-Demethylepipodophyllotoxin (product 1) was then biotransformed into 4'-demethylpodophyllotoxone (product 2) with the oxidation of the hydroxyl group at the 4 position by Alternaria alternata S-f6, which was screened out from the gathered Dysosma versipellis plants in the Wuhan Botanical Garden, Chinese Academy of Sciences. Finally, 4'-demethylpodophyllotoxone (product 2) and ligustrazine were linked with a transamination reaction to synthesize the target product 4-TMP-DMEP (product 3) by Alternaria alternata S-f6. Compared with podophyllotoxin (i.e., a 50% effective concentration [EC(50)] of 529 mu M), the EC50 of 4-TMP-DMEP against the tumor cell line BGC-823 (i.e., 0.11 mu M) was significantly reduced by 5,199 times. Simultaneously, the EC50 of 4-TMP-DMEP against the normal human proximal tubular epithelial cell line HK-2 (i. e., 0.40 mu M) was 66 times higher than that of podophyllotoxin (i. e., 0.006 mu M). Furthermore, compared with podophyllotoxin (i. e., log P = 0.34), the water solubility of 4-TMP-DMEP (i. e., log P = 0.66) was significantly enhanced by 94%. For the first time, the novel compound 4-TMP-DMEP with superior antitumor activity was directionally synthesized from podophyllotoxin by the novel tandem biotransformation process developed in this work.
KeywordTruffle Tuber-sinense Polysaccharides Production Biological Evaluation Gibberella-fujikuroi Anticancer Agents Natural-products Cell-growth Podophyllotoxin Derivatives 4'-demethylepipodophyllotoxin
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1128/AEM.03047-10
Indexed BySCI
Language英语
WOS KeywordTRUFFLE TUBER-SINENSE ; POLYSACCHARIDES PRODUCTION ; BIOLOGICAL EVALUATION ; GIBBERELLA-FUJIKUROI ; ANTICANCER AGENTS ; NATURAL-PRODUCTS ; CELL-GROWTH ; PODOPHYLLOTOXIN ; DERIVATIVES ; 4'-DEMETHYLEPIPODOPHYLLOTOXIN
WOS Research AreaBiotechnology & Applied Microbiology ; Microbiology
WOS SubjectBiotechnology & Applied Microbiology ; Microbiology
WOS IDWOS:000289773100026
Citation statistics
Cited Times:10[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Version出版稿
Identifierhttp://ir.ipe.ac.cn/handle/122111/5049
Collection生化工程国家重点实验室
Corresponding AuthorTang, YJ
Affiliation1.Hubei Univ Technol, Coll Bioengn, Minist Educ, Hubei Prov Key Lab Ind Microbiol,Key Lab Fermenta, Wuhan 430068, Peoples R China
2.Chinese Acad Sci, Shanghai Adv Res Inst, Lab Biorefinery Engn, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100080, Peoples R China
4.E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China
Recommended Citation
GB/T 7714
Tang, Ya-Jie,Zhao, Wei,Li, Hong-Mei,et al. Novel Tandem Biotransformation Process for the Biosynthesis of a Novel Compound, 4-(2,3,5,6-Tetramethylpyrazine-1)-4 '-Demethylepipodophyllotoxin[J]. APPLIED AND ENVIRONMENTAL MICROBIOLOGY,2011,77(9):3023-3034.
APA Tang, Ya-Jie,Zhao, Wei,Li, Hong-Mei,&Tang, YJ.(2011).Novel Tandem Biotransformation Process for the Biosynthesis of a Novel Compound, 4-(2,3,5,6-Tetramethylpyrazine-1)-4 '-Demethylepipodophyllotoxin.APPLIED AND ENVIRONMENTAL MICROBIOLOGY,77(9),3023-3034.
MLA Tang, Ya-Jie,et al."Novel Tandem Biotransformation Process for the Biosynthesis of a Novel Compound, 4-(2,3,5,6-Tetramethylpyrazine-1)-4 '-Demethylepipodophyllotoxin".APPLIED AND ENVIRONMENTAL MICROBIOLOGY 77.9(2011):3023-3034.
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