Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Stereoselective Biotransformation of Timosaponin A-III by Saccharomyces cerevisiae

  • Hu, Yong-Mei (Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University) ;
  • Yu, Zhi-Ling (Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University) ;
  • Fong, Wang-Fun (Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University)
  • Received : 2011.01.03
  • Accepted : 2011.03.15
  • Published : 2011.06.28
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Abstract

Bioconversion of timosaponin A-III (TA-III), one of the major steroidal saponins isolated from the rhizomes of Anemarrhenae asphodeloides Bunge (Liliaceae), was investigated in Saccharomyces cerevisiae. Five bioconversion products, denoted compounds 2-6, were obtained. Biotransformation metabolite 2 was a stereoisomer of TAIII with a specific isotype F-ring and ${\beta}$-ranged $CH_3$-21, which rarely occurs in nature. The structure of 2 was elucidated by extensive spectroscopic analysis (H-H COSY, HSQC, HMBC), as well as by high-resolution mass spectral analysis. The growth inhibitory activity of compounds 1-6 was assayed against four human cancer cell lines, HepG2, H-1299, HT-29, and HCT-116. Compounds 1 and 2 obviously inhibited the growth of the four types of cancer cells with $IC_{50}$ values being less than 19${\mu}M$. A structure-activity relationship is discussed, and the spirostane-ring F in compounds 1 and 2 appears to be the critical bioactive moiety for the cell growth inhibitory property.

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References

  1. Agrawa, P. K., D. C. Jain, P. K. Gupta, and R. S. Thakur. 1985. Carbon-13 NMR spectroscopy of steroidal sapogenin and steroidal saponins. Phytochemistry 24: 2479-2496. https://doi.org/10.1016/S0031-9422(00)80653-6
  2. Agrawa, P. K., D. C. Jain, and A. K. Pathak. 1995. NMR spectroscopy of steroidal sapogenins and steroidal saponins: An update. Magn. Reson. Chem. 33: 923-953. https://doi.org/10.1002/mrc.1260331202
  3. Aharonowitz, Y. and G. Cohen. 1981. The microbiological production of pharmaceuticals. Sci. Am. 245: 140-152.
  4. Bomi, L., K. Jun, and D. H. Kim. 2009. Timosaponin AIII, a saponin isolated from Anemarrhena asphodeloides, ameliorates learning and memory deficits in mice. Pharmacol. Biochem. Behav. 93: 121-127. https://doi.org/10.1016/j.pbb.2009.04.021
  5. Bao, W. N., H. F. Pan, M. Lu, Y. Ni, R. Zhang, and X. G. Gong. 2007. The apoptotic effect of sarsasapogenin from Anemarrhena asphodeloides on HepG2 human hepatoma cells. Cell Biol. Int. 31: 887-892. https://doi.org/10.1016/j.cellbi.2007.02.001
  6. Csuk, R. and B. I. Glanzer. 1991. Baker's yeast mediated transformations in organic chemistry. Chem. Rev. 91: 49-97. https://doi.org/10.1021/cr00001a004
  7. Debella, A., E. Haslinger, Q. Kunert, G. Michl, and D. Abebe. 1999. Steroidal saponins from Asparagus africanus. Phytochemistry 51: 1069-1075. https://doi.org/10.1016/S0031-9422(99)00051-5
  8. Devon, T. K. and A. I. Scott. 1972. Handbook of Naturally Occurring Compounds, Vol. II, Terpenes, pp. 404-411. Academic Press, NY. 1972.
  9. Dong, J. X. and G. Y. Han 1991. A new active steroidal saponin from Anemarrhena asphodeloides. Planta Med. 57: 460-462. https://doi.org/10.1055/s-2006-960151
  10. Dong, J. X. and G. Y. Han. 1992. Studies on the active constituents of Anemarrhena asphodeloides Bunge. Yao Xue Xue Bao 27: 26-32.
  11. Eveleigh, D. E. 1981. The microbiological production of industrial chemicals. Sci. Am. 245: 154-178.
  12. Feng, B., S. Q. Wang, and B. P. Ma. 2005. Study on biotransformation of steroidal saponins and its specific glycosidase. Dissertation of Doctor Degree of China Military Medical Science Institute, pp. 29-40.
  13. Hamada, H., Y. Miyamoto, N. Nakajima, and T. Furuya. 1998. Lipase-mediated asymmetric acetylation of prochiral diols directed towards total syntheses of biologically active molecules. J. Mol. Catal. B Enzym. 5: 187-189. https://doi.org/10.1016/S1381-1177(98)00032-0
  14. Hu, Y. E., Z. Q. Xia, Q. X. Sun, A. Orisi, and D. Rees. 2005. A new approach to the pharmacological regulation of memory: Sarsasapogenin improves memory by elevating the low muscarinic acetylcholine receptor density in brains of memory-deficit rat models. Brain Res. 1060: 26-39. https://doi.org/10.1016/j.brainres.2005.08.019
  15. King, F. W., S. Fong, C. Griffin, M. Shoemaker, R. Staub, Y. L. Zhang, I. Cohen, and E. Shtivelman. 2009. Timosaponin AIII is preferentially cytotoxic to tumor cells through inhibition of mTOR and induction of ER stress. PLoS ONE 4: 7283. https://doi.org/10.1371/journal.pone.0007283
  16. Kaoru, N., I. Kiyoko, U. Kazutoshi, O. Shinzaburo, and O. Atsuyoshi. 1988. Stereochemical control on yeast reduction of $\alpha$-keto esters. Reduction by immobilized Bakers' yeast in hexane. J. Org. Chem. 53: 2589-2593. https://doi.org/10.1021/jo00246a035
  17. Miyazawa, M. and M. Ohsawa. 2002. Biotransformation of $\alpha$- terpineol by the larvae of common cutworm (Spodoptera litura). J. Agric. Food Chem. 50: 4916. https://doi.org/10.1021/jf020287e
  18. Ni, Y., X. G. Gong, M. Lu, H. M. Chen, and Y. Wang. 2008. Mitochondrial ROS burst as an early sign in sarsasapogenininduced apoptosis in HepG2 cells. Cell Biol. Int. 32: 337-343. https://doi.org/10.1016/j.cellbi.2007.12.004
  19. Nian, H., L. P. Qin, W. S. Chen, Q. Y. Zhang, H. C. Zheng, and Y. Wang. 2006. Protective effect of steroidal saponins from rhizomes of Anemarrhena asphodeloides on ovariectomy-induced bone loss in rats. Acta Pharmacol. Sin. 27: 728-734. https://doi.org/10.1111/j.1745-7254.2006.00328.x
  20. Niwa, A., O. Takeda, M. Ishimaru, Y. Nakamoto, K. Yamasaki, H. Kohda, et al. 1988. Screening test for platelet aggregation inhibitor in natural products. The active principle of Anemarrhenae rhizoma. Yakugaku Zasshi 108: 555-561.
  21. Saito, S., S. Nagase, and K. Ichinose. 1994. New steroidal saponins from the rhizomes of Anemarrhena asphodeloides Bunge (Liliaceae). Chem. Pharm. Bull. 42: 2342-2345. https://doi.org/10.1248/cpb.42.2342
  22. Shimoda, K., S. Y. Yamane, H. Hirakawa, S. Ohta, and T. Hirata. 2002. Biotransformation of phenolic compounds by the cultured cells of Catharanthus roseus. J. Mol. Catal. B Enzym. 16: 275- 279. https://doi.org/10.1016/S1381-1177(01)00073-X
  23. Tomas, H., T. Toshiya, and G. G. Kumar. 1991. Yeast-mediated resolution of $\beta$-keto esters of prochiral alcohols. J. Org. Chem. 56: 3619-3623. https://doi.org/10.1021/jo00011a031
  24. Skenhan, P., R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, et al. 1990. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 82: 1107-1112. https://doi.org/10.1093/jnci/82.13.1107
  25. Sy, L. K., S. C. Yan, C. N. Lok, R. Y. Man, and C. M. Che. 2008. Timosaponin A-III induces autophagy preceding mitochondriamediated apoptosis in HeLa cancer cells. Cancer Res. 68: 10229-10237. https://doi.org/10.1158/0008-5472.CAN-08-1983
  26. Takahashi, M., C. Komo, and H. Hikino. 1985. Isolation and hypoglycemic activity of anemarans A, B, C, and D, glycans of Anemarrhena asphodeloides rhizomes. Planta Med. 51: 100-102. https://doi.org/10.1055/s-2007-969417
  27. Tobari, A., M. Teshima, J. Koyanagi, M. Kawase, H. Miyamae, K. Yoza, A. Takasaki, Y. Nagamura, and S. Saito, 2000. Spirostanols obtained by cyclization of pseudosaponin derivatives and comparison of anti-platelet agglutination activities of spirostanol glycosides. Eur. J. Med. Chem. 35: 511-527. https://doi.org/10.1016/S0223-5234(00)00151-3
  28. Wall, M. E., C. R. Eddy, and S. Serota. 1954. Steroidal sapogenins. XIX. Stereochemistry of sapogenins and cholesterol at carbon 20. J. Am. Chem. Soc. 76: 2849-2850. https://doi.org/10.1021/ja01639a086
  29. Wall, M. E. and S. Serota. 1954. Steroidal sapogenins. XX. Configuration of spiroketal side chain at carbon 22. J. Am. Chem. Soc. 76: 2850-2852. https://doi.org/10.1021/ja01639a087
  30. Wall, M. E., C. R. Eddy, and S. Serota. 1955. Steroidal sapogenins. XVIII. Partial hydrolysis of steroidal saponins of Yucca schidigera. J. Am. Chem. Soc. 77: 1230. https://doi.org/10.1021/ja01610a040
  31. Zhang, Y. H., Y. L. Wu, S. I. Tashiro, S. Onodera, and T. Ikejima. 2009. Involvement of PKC signal pathways in oridonin-induced autophagy in HeLa cells: A protective mechanism against apoptosis. Biochem. Biophys. Res. Commun. 378: 273-278. https://doi.org/10.1016/j.bbrc.2008.11.038
  32. Zhang, J. Y., Z. Y. Meng, M. Y. Zhang, D. S. Ma, S. X. Xu, and H. Kodama. 1999. Effect of six steroidal saponins isolated from Anemarrhenae rhizoma on platelet aggregation and hemolysis in human blood. Clin. Chim. Acta 289: 79-88. https://doi.org/10.1016/S0009-8981(99)00160-6
  33. Zubay, G. 1989. Biochemistry, 2nd Ed. Macmillan Publishing Company, New York.

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