Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Production and Characterization of Antihypertensive Angiotensin I-Converting Enzyme Inhibitor from Pholiota adiposa

  • Koo Kyo-Chul (Department of Life Science and Genetic Engineering, Paichai University) ;
  • Lee Dae-Hyoung (Department of Life Science and Genetic Engineering, Paichai University) ;
  • Kim Jae-Ho (Bae Sang Myun Brewery Co., Ltd.) ;
  • Yu Hyung-Eun (Department of Life Science and Genetic Engineering, Paichai University) ;
  • Park Jeong-Sik (Institute of Agricultural Science and Technology) ;
  • Lee Jong-Soo (Department of Life Science and Genetic Engineering, Paichai University)
  • Published : 2006.05.01
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Abstract

Angiotensin I-converting enzyme (ACE) inhibitors have generally been very useful to remedy or prevent hypertension. This study describes the extraction and characterization of an ACE inhibitor from the fruiting body of Pholiota adiposa ASI 24012, which can be used as an antihypertensive drug. The maximal ACE inhibitory activity $(IC_{50};0.25mg)$ was obtained when the fruiting body of Pholiota adiposa ASI 24012 was extracted with distilled water at $30^{\circ}C$ for 12 h. After the purification of ACE inhibitor with ultrafiltration, Sephadex G-25 column chromatography, and reverse-phase HPLC, an active fraction with an $IC_{50}$ of 0.044 mg was obtained. The purified ACE inhibitory peptide was a novel pentapeptide, showing very little similarity to other ACE inhibitory peptide sequences. The molecular mass of the purified ACE inhibitor was estimated to be 414 daltons with a sequence of Gly-Glu-Gly-Gly-Pro, and showed a clear antihypertensive effect on spontaneously hypertensive rats (SHR) at a dosage of 1 mg/kg.

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References

  1. Arihara, K., Y. Nakashima, T. Mukai, S. Ishikawa, and M. Itoh. 2001. Peptide inhibitors for angiotensin I-converting enzyme from enzymatic hydrolysates of porcine skeletal muscle proteins. Meat Sci. 57: 319-324 https://doi.org/10.1016/S0309-1740(00)00108-X
  2. Ariyosh, Y. 1993. Angiotensin converting enzyme inhibitors derived from food protein. Trends Food Sci. Technol. 4: 139-144 https://doi.org/10.1016/0924-2244(93)90033-7
  3. Astawan, M., M. Wahyuni, T. Yasuhara, K. Yamada, T. Tadokoro, and A. Maekawa. 1995. Effects of angiotensin-I converting enzyme inhibitory substance derived from Indonesian dried-salted fish on blood pressure of rats. Biosci. Biotechnol. Biochem. 59: 425-429 https://doi.org/10.1271/bbb.59.425
  4. Athukorala, Y. and Y. J. Jeon. 2005. Screening for angiotensin I-converting enzyme inhibitory activity of Ecklonia cava. Korean J. Food Sci. Nutr. 10: 134-139 https://doi.org/10.3746/jfn.2005.10.2.134
  5. Choi, H. S., H. Y. Cho, H. C. Yang, K. S. Ra, and H. J. Suh. 2001. Angiotensin I-converting enzyme inhibitor from Grifola frondosa. Food Res. Int. 34: 177-182 https://doi.org/10.1016/S0963-9969(00)00149-6
  6. Cheung, H. S., F. L. Wang, M. A. Ondetti, E. F. Sabo, and D. W. Cushman. 1980. Binding of peptide substrates and inhibitors of angiotensin-converting enzyme. Importance of the COOH-terminal dipeptide sequence. J. Biol. Chem. 255: 401-407
  7. Cushman, D. W. and H. S. Cheung. 1971. Spectrophotometric assay and properties of the angiotensin converting enzyme of rabbit lung. Biochem. Pharmacol. 20: 1637-1648 https://doi.org/10.1016/0006-2952(71)90292-9
  8. Demain, A. L., G. A. Somkuti, J. C. Hunter-Cevera, and H. W. Rossmoore. 1989. Novel Microbial Products for Medicine and Agriculture. Elsevier Science Publisher Co.
  9. Ferreira, S. H., D. C. Bartelt, and L. J. Greene. 1970. Isolation of bradykinin-potentiating peptides from Bothrops jararaca venom. Biochemistry 9: 2583-2592 https://doi.org/10.1021/bi00815a005
  10. Folkow, B., B. Johansson, and S. Mellander. 1961. The comparative effects of angiotensin and noradrenaline on consecutive vascular sections. Acta Physiol. Scand. 53: 99-104 https://doi.org/10.1111/j.1748-1716.1961.tb02267.x
  11. Fujita, H. and M. Yoshikawa. 1999. A prodrug-type ACE-inhibitory peptide derived from fish protein. Immunopharmacology 44: 123-127 https://doi.org/10.1016/S0162-3109(99)00118-6
  12. Jeong, S. C., S. P. Cho, B. K. Yang, Y. T. Jeong, K. S. Ra, and C. H. Song. 2004. Immunomodulating activity of the exopolymer from submerged mycelial culture of Phellinus pini. J. Microbiol. Biotechnol. 14: 15-21
  13. Kim, J. H., D. H. Lee, S. Y. Choi, and J. S. Lee. 2002. Characterization of physiological functionalities in Korean traditional liquors. Korean Food Sci. Technol. 34: 118-122
  14. Kim, J. H., D. H. Lee, S. C. Jeong, K. S. Chung, and J. S. Lee. 2004. Characterization of antihypertensive angiotensin I-converting enzyme inhibitor from S. cerevisiae. J. Microbiol. Biotechnol. 14: 1318-1323
  15. Kim, K. B., S. I. Kim, and K. S. Song. 2003. Neuraminidase inhibitors from mushroom Microphorus affinis. J. Microbiol. Biotechnol. 13: 778-782
  16. Kim, H. H., J. G. Na, Y. K. Chang, G. T. Chun, S. J. Lee, and Y. H. Jeong. 2004. Optimization of submerged culture conditions for mycelial growth and exopolysaccharides production by Agaricus blazei. J. Microbiol. Biotechnol. 14: 944-951
  17. Kohama, Y., Y. Nagase, H. Oka, T. Nakagama, T. Teramoto, N. Murayama, H. Tsujibo, Y. Inamori, and T. Mimura. 1990. Production of angiotensin-converting enzyme inhibitors from Baker's yeast glyceraldehyde-3-phosphate dehydrogenase. J. Pharmacobio-Dyn. 13: 766-771 https://doi.org/10.1248/bpb1978.13.766
  18. Lee, D. H., J. H. Kim, J. C. Cheang, W. S. Gong, Y. B. Yoo, J. J. Park, C. H. Yoo, and J. S. Lee. 2003. Screening of mushrooms having antihypertensive angiotensin I-converting enzyme inhibitor. Korea J. Mycol. 3: 148-154
  19. Lee, D. H., J. H. Kim, J. S. Park, C. H. Yoo, and J. S. Lee. 2004. Isolation and characterization of a novel angiotensin Iconverting enzyme inhibitory peptide derived from the edible mushroom Tricholoma giganteum. Peptides 25: 621-627 https://doi.org/10.1016/j.peptides.2004.01.015
  20. Marczak, E. D., H. Usui, H. Fujita, Y. Yang, M. Yokoo, A. W. Lipkowski, and M. Yoshikawa. 2003. New antihypertensive peptides isolated from rapeseed. Peptides. 24: 791-798 https://doi.org/10.1016/S0196-9781(03)00174-8
  21. Maruyama, S., S. Miyoshi, and H. Tanaka. 1989. Angiotensin converting enzyme inhibitor derived from Ficus carica. Agric. Biol. Chem. 53: 2763-2769 https://doi.org/10.1271/bbb1961.53.2763
  22. Miyoshi, S., H. Ishikawa, T. Kaneko, F. Fukui, H. Tanaka, and S. Maruyama. 1991. Structures and activity of angiotensinconverting enzyme inhibitors in an {\alpha}$-zein hydrolysate. Agric. Biol. Chem. 55: 1313-1318 https://doi.org/10.1271/bbb1961.55.1313
  23. Morigiwa, A., A. Kitabatake, Y. Fujimoto, and N. Ikekawa. 1986. Angiotensin converting enzyme inhibitory triterpenes from G. lucidum. Chem. Pharmaceut. Bull. 34: 3025-3028 https://doi.org/10.1248/cpb.34.3025
  24. Ondetti, M. A., B. Rubin, and D. W. Cushman. 1982. Enzyme of the renin-angiotensin system and their inhibitors. Annu. Rev. Biochem. 51: 283-308 https://doi.org/10.1146/annurev.bi.51.070182.001435
  25. Park, J. S., K. W. Hyun, S. B. Seo, S. M. Cho, C. H. Yoo, and J. S. Lee. 2003. Detection of platelet aggregation inhibitors and fibrinolytic substances from mushrooms. Korea J. Mycol. 31: 114-116 https://doi.org/10.4489/KJM.2003.31.2.114
  26. Rhyu, M. R., Y. J. Nam, and H. Y. Lee. 1996. Screening of angiotensin converting enzyme inhibitors in cereals and legumes. Foods Biotechnol. 5: 334-337
  27. Saito, Y., K. Wanezaki, A. Kawato, and S. Imayasu. 1992. Angiotensin-I converting enzyme inhibitor in sake and its by-product. Nippon Nogeikagaku Kaishi 66: 1081-1087 https://doi.org/10.1271/nogeikagaku1924.66.1081
  28. Saito, Y., K. Wanezaki, A. Kawato, and S. Imayasu. 1994. Structure and activity of angiotensin I converting enzyme inhibitory peptides from sake and sake lees. Biosci. Biotechnol. Biochem. 58: 767-1771
  29. Sugiyama, K., K. Takada, M. Egawa, I. Yamamoto, H. Onzuka, and K. Oba. 1991. Hypertensive effect of fish protein hydrolysate. Nippon Nogeikagaku Kaishi 65: 35-41 https://doi.org/10.1271/nogeikagaku1924.65.35
  30. Sun, H. J., S. J. Cho, J. H. Whang, H. Lee, and H. C. Yang. 1997. Characterization of angiotensin converting enzyme inhibitor from squid hydrolysate. Foods Biotechnol. 6: 122-128
  31. Totowa, N. J. 1994. Basic Protein and Peptide Protocols. Humana Press, New Jersey, U.S.A
  32. Yang, B. K., M. A. Wilson, K. Y. Cho, and C. H. Song. 2004. Hypoglycemic effect of exo- and endo-biopolymers produced by submerged mycelial culture of Ganoderma lucidum in streptozotocin-induced diabetic rats. J. Microbiol. Biotechnol. 14: 972-977
  33. Yokoyama, K., H. Chiba, and M. Yoshikawa. 1992. Peptide inhibitors for angiotensin I-converting enzyme from thermolysin digest of dried bonito. Biosci. Biotech. Biochem. 56: 1541-1545 https://doi.org/10.1271/bbb.56.1541
  34. Zhao, M. W., J. Y. Zhong, W. Q. Liang, N. Wang, M. J. Chen, D. B. Zhang, Y. J. Pan, and S. C. Jong. 2004. Analysis of squalene synthase expression during the development of Ganoderma lucidum. J. Microbiol. Biotechnol. 14: 116-120