A novel biotransformation process of 4′-demethylepipodophyllotoxin to 4′-demethylepipodophyllic acid by Bacillus fusiformis CICC 20463, Part II: process optimization

Tang, Ya‐Jie; Xu, Xiaoling; Zhong, Jian‐Jiang

doi:10.1007/s00449-009-0317-x

Cited by 7 publications

(7 citation statements)

References 26 publications

(26 reference statements)

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“…Similar results were obtained with Hordeum vulgare cell cultures, in which PTOX was bioconverted into isopicropodophyllone [76]. 4 0 -Demethylepipodophyllic acid has shown impressive activity against most of the colon and breast cancer cell lines, probably because it is more water-soluble than DMEP [77]. This compound has recently been biotransformed into the more soluble derivative 4 0 -demethylepipodophyllic acid by Bacillus fusiformis cultures [77].…”

Section: Biotransformationsupporting

confidence: 71%

“…Thus, biotransformation based on plant cells or microbes can offer a useful tool for producing new compounds with the advantage of high stereo-and regioselectivity, mild reaction conditions, and simple operation procedures compared with chemical modification [74]. This compound has recently been biotransformed into the more soluble derivative 4 0 -demethylepipodophyllic acid by Bacillus fusiformis cultures [77]. Similar results were obtained with Hordeum vulgare cell cultures, in which PTOX was bioconverted into isopicropodophyllone [76].…”

Section: Biotransformationmentioning

confidence: 60%

“…In the last decade, the PTOX derivative 4 0 -demethylepipodophyllotoxin has attracted considerable attention as a raw material for the semi-synthesis of anticancer drugs. This compound has recently been biotransformed into the more soluble derivative 4 0 -demethylepipodophyllic acid by Bacillus fusiformis cultures [77]. Similarly, P. aeruginosa cultures can convert PTOX into picropodophyllotoxin and podophyllic acid, the latter being used as a leading compound to synthesize hydrazide derivatives with stronger anticancer and antioxidative activity [16].…”

Section: Biotransformationmentioning

confidence: 99%

“…The same authors report obtaining 4 0 -demethylepipodophyllic acid by the biotransformation of 4 0 demethylepipodophyllotoxin (DMEP) by B. fusiformis c ultures. 4 0 -Demethylepipodophyllic acid has shown impressive activity against most of the colon and breast cancer cell lines, probably because it is more water-soluble than DMEP [77]. Biotransformation of DOP to epipodophyllotoxin by human hepatic enzymes CYP1A1, CYP2C9, and CYP3A4 herelologously expressed in E. coli has been reported, showing that CYP3A4 catalyses this hydroxylation with high efficiency (90%) [78].…”

Section: Biotransformationmentioning

confidence: 99%

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Podophyllotoxin: Current approaches to its biotechnological production and future challenges

Yousefzadi¹,

Sharifi²,

Behmanesh³

et al. 2010

Engineering in Life Sciences

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Many plant‐derived agents are being used to treat cancer, including taxol, vinblastine, vincristine, or camptothecin and podophyllotoxin derivatives, among others. Plant biotechnology can provide a new tool for the production of anticancer agents but in spite of considerable efforts to produce vinblastine and vincristine in cell cultures and knowledge of the biosynthetic pathway of Catharanthus roseus alkaloids, the biotechnological production of taxol has only been achieved at an industrial level by companies such as Phyton Biotech and Cytoclonal Pharmaceutics. Podophyllotoxin was isolated as the active antitumor agent from the roots of Podophyllum species and more recently from the genus Linum and others. Etoposide, teniposide, and etophos are semi‐synthetic derivatives of podophyllotoxin and are used in the treatment of cancer. Biotechnological approaches, including the use of cell cultures, biotransformation, or metabolic engineering techniques to manipulate the biosynthetic pathway, represent an alternative for the production of podophyllotoxin and are discussed in this review.

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Section: Biotransformationsupporting

confidence: 71%

Section: Biotransformationmentioning

confidence: 60%

Section: Biotransformationmentioning

confidence: 99%

Section: Biotransformationmentioning

confidence: 99%

See 2 more Smart Citations

Podophyllotoxin: Current approaches to its biotechnological production and future challenges

Yousefzadi¹,

Sharifi²,

Behmanesh³

et al. 2010

Engineering in Life Sciences

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“…In our previous work, PTOX was hydrolyzed and isomerized to produce podophyllic acid and picropodophyllotoxin by Pseudomonas aeruginosa CCTCC AB93066 [22,23]. 4 -demethylepipodophyllotoxin (DMEP) was biotransformed into 4 -demethylpodophyllic acid with a hydrolysis reaction by Bacillus fusiformis CICC20463 [24,25]. Furthermore, a novel tandem biotransformation process was developed for the directional modification of PTOX structure to biosynthesize a novel compound, 4-(2,3,5,6-tetramethylpyrazine-1)-4 -demethylepipodophyllotoxin with superior activity against the tumor cell line BGC-823 [26].…”

Section: Introductionmentioning

confidence: 99%

Novel Biotransformation Process of Podophyllotoxin to 4 -Sulfur-Substituted Podophyllum Derivates with Anti-Tumor Activity by Penicillium purpurogenum Y.J. Tang

Bai¹,

Zhao²,

Li³

et al. 2012

CMC

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According to the structure-function relationship of podophyllotoxin (PTOX) and its analogue of 4'- demethylepipodophyllotoxin (DMEP), the 4 β-substitution of sulfur-containing heterocyclic compounds with a carbon-sulfur bond at 4 position of PTOX or DMEP is an essential modification direction for improving the anti-tumor activity. So, four novel 4 β-sulfursubstituted podophyllum derivatives (i.e., 4β -(1,2,4-triazole-3-yl)sulfanyl-4-deoxy-podophyllotoxin (4-MT-PTOX), 4β-(1,3,4- thiadiazole-2-yl)sulfanyl-4-deoxy-podophyllotoxin (4-MTD-PTOX), 4β-(1,2,4-triazole-3-yl)sulfanyl-4-deoxy-4' -demethylepipodophyllotoxin (4-MT-DMEP), and 4β-(1,3,4-thiadiazole-2-yl)sulfanyl-4-deoxy-4'-demethylepipodophyllotoxin (4-MTD-DMEP)) were designed and then successfully biosynthesized in this work. In the novel sulfur-substituted biotransformation processes, PTOX and DMEP was linked with sulfur-containing compounds (i.e., 3-mercapto-1,2,4-triazole (MT) and 2-mercapto-1,3,4-thiadiazole (MTD)) at 4 position of cycloparaffin to produce 4-MT-PTOX (1), 4-MTD-PTOX (2), 4-MT-DMEP (3), and 4-MTD-DMEP (4) by Penicillium purpurogenum Y.J. Tang, respectively, which was screened out from Diphylleia sinensis Li (Hubei, China). All the novel compounds exhibited promising in vitro bioactivity, especially 4-MT-PTOX (1). Compared with etoposide (i.e., a 50 % effective concentration [EC(50)] of 25.72, 167.97, and 1.15 M), the EC(50) values of 4-MT-PTOX (1) against tumor cell line BGC-823, A549 and HepG2 (i.e., 0.28, 0.76, and 0.42 M) were significantly improved by 91, 221 and 2.73 times, respectively. Moreover, the EC(50) value of 4-MT-PTOX (1) against the normal human cell line HK-2 (i.e., 182.4 μM) was 19 times higher than that of etoposide (i.e., 9.17 μM). Based on the rational design, four novel 4 β-sulfur-substituted podophyllum derivatives with superior in vitro anti-tumor activity were obtained for the first time. The correctness of structure-function relationship and rational drug design was strictly demonstrated by the in vitro biological activity tests.

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Electrochemical Biosensor Based on Nanocomposites Film of Thiol Graphene‐Thiol Chitosan/Nano Gold for the Detection of Carcinoembryonic Antigen

Li¹,

Xue²,

Feng³

et al. 2015

Electroanalysis

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In this paper, a thiol graphene‐thiol chitosan‐gold nanoparticles (thGP‐thCTS‐AuNPs) nanocomposites film with porous structure was fabricated by electrochemically depositing on glassy carbon electrode (GCE), which exhibited good biocompatibility and improved conductivity, to construct immunosensor free label for detection of carcinoembryonic antigen (CEA). The electrochemical behavior of this immunosensor was investigated by cyclic voltammetry. Under the optimum conditions, the immunosensor revealed a good amperometric response to CEA in two linear ranges (0.3–8.0 ng mL−1 and 8.0–100 ng mL−1) with a detection limit of 0.03 ng mL−1. The results indicated that the immunosensor has the advantages of good selectivity, high sensitivity, and good stability for the determination of CEA.

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A novel biotransformation process of 4′-demethylepipodophyllotoxin to 4′-demethylepipodophyllic acid by Bacillus fusiformis CICC 20463, Part II: process optimization

Cited by 7 publications

References 26 publications

Podophyllotoxin: Current approaches to its biotechnological production and future challenges

Podophyllotoxin: Current approaches to its biotechnological production and future challenges

Novel Biotransformation Process of Podophyllotoxin to 4 -Sulfur-Substituted Podophyllum Derivates with Anti-Tumor Activity by Penicillium purpurogenum Y.J. Tang

Electrochemical Biosensor Based on Nanocomposites Film of Thiol Graphene‐Thiol Chitosan/Nano Gold for the Detection of Carcinoembryonic Antigen

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