Characterization of Antihypertensive Angiotensin I-Converting Enzyme Inhibitor from Saccharomyces cerevisiae

  • KIM, JAE-HO (Bae Sang Myun Brewery Co., Ltd.) ;
  • LEE, DAE-HYOUNG (Department of Genetic Engineering and Bio-Medical Resource Research Center, Paichai University) ;
  • JEONG, SEOUNG-CHAN (Department of Genetic Engineering and Bio-Medical Resource Research Center, Paichai University) ;
  • CHUNG, KUN-SUB (Department of Biological Resources and Technology, Yonsei University) ;
  • LEE, JONG-SOO (Department of Genetic Engineering and Bio-Medical Resource Research Center, Paichai University)
  • Published : 2004.12.01


This study describes the purification and characterization of a novel antihypertensive angiotensin 1­converting enzyme (ACE) inhibitory peptide from Saccharomyces cerevisiae. Maximal production of the ACE inhibitor from Saccharomyces cerevisiae was obtained from 24 h of cultivation at $30^{\circ}C$ and its ACE inhibitory activity was increased by about 1.5 times after treatment of the cell-free extract with pepsin. After the purification of ACE inhibitory peptides with ultrafiltration, Sephadex G-25 column chromatography, and reverse-phase HPLC, an active fraction with an $IC_{50}$ of 0.07 mg and $3.5\%$ yield was obtained. The purified peptide was a novel decapeptide, showing very low similarity to other ACE inhibitory peptide sequences, and its amino acid sequence was Tyr-Asp-Gly-Gly-Val-Phe-Arg-Val-Tyr-Thr. The purified inhibitor competitively inhibited ACE and also showed a clear antihypertensive effect in spontaneously hypertensive rats (SHR) at a dosage of 1 mg/kg body weight.



  1. Ando, T., S. Okada, I. Uchida, K. Hemmi, M. Nishikawa, Y. Tsurumi, A. Fujie, K. Yoshida, and M. Okuhara. 1987. WF-10129, a novel angiotensin converting enzyme inhibitor produced by a fungus, Doratomyces putredinis. J. Antibiot. 40: 468-475
  2. Ando, T., Y. Tsurumi, N. Ohata, I. Uchida, K. Yoshida, and M. Okuhara. 1988. Vinigrol, a novel antihypertensive and platelet aggregation inhibitory agent produced by a fungus, Virgaria nigra. Taxonomy, fermentation, isolation, physico-chemical and biological properties. J. Antibiot. 41: 25-30
  3. Ariyosh. Y. 1993. Angiotensin-converting enzyme inhibitors derived from food proteins. Trends Food Science Technol. 4: 139-144
  4. Bae, E. A., M. J. Han, M. J. Song, and D. H. Kim. 2002. Purification of rotavirus infection-inhibitory protein from Bifidobacterium breve K-110. J. Microbiol. Biotechnol. 12: 553-556
  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 Research International 34: 177-182
  6. Cushman, D. W., H. S. Cheung, E. F. Sabo, and M. A. Ondetti. 1977. Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxylalkanoyl and mercaptoalkanoyl amino acids. Biochemistry 16: 54-84
  7. Elisseeva, Y. E., V. N. Orekhovich, L. N. Pavlikhina, and L. P. Alexeenko. 1971. Carboxycathepsin - A key regulatory component of two physiological systems involved in regulation of blood pressure. Clin. Chim. Acta 31: 413- 419
  8. Fujita, H., K. Yokoyama, and M. Yoshikawa. 2000. Classification and antihypertensive activity of angiotensin I-converting enzyme inhibitory peptides derived from food proteins. J. Food Sci. 65: 564-569.
  9. Funayama, S. and H. Hikino. 1979. Hypotensive principles of Diospyros kaki leaves. Chem. Pharm. Bull. 25: 456- 460
  10. Gohlke, P., W. Linz, B. A. Schokens, I. Kuwer, S. Bartenbach, A. Schell, and T. Unger. 1994. Angiotensin converting enzyme inhibition improves cardiac function. Hypertension 23: 411-418
  11. Kido, Y., T. Hamakado, T. Yoshida, M. Anno, Y. Motoki, T. Wakamiya, and T. Shiba. 1983. Isolation and characterization of ancovenin, a new inhibitor of angiotensin I converting enzyme produced by Actinomycetes. J. Antibiot. 36: 1295- 1299
  12. Kim, J. H., D. H. Lee, S. Y. Choi, and J. S. Lee. 2002. Characterization of physiological functionalities in Korean tradition liquors. Korea J. Food Sci. Technol. 34: 118-122
  13. 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
  14. Lee, D. H., W. S. Gong, Y. B. Yoo, J. J. Park, C. H. Yoo, and J. S. Lee. 2003. Screening of antihypertensive angiotensin I-converting enzyme inhibitor from mushrooms. Korea J. Mycol. 31: 148-154
  15. Lee, D. H., J. H. Kim, J. S. Park, C. H. Yoo, and J. S. Lee. 2004. Isolation and characterization of a novel angiotensin I-converting enzyme inhibitory peptide derived from the edible mushroom Tricholoma giganteum. J. Peptides 4: 621-627
  16. Lee, J. S., S. H. Yi, S. J. Kwon, C. Ahn, and J. Y. Yoo. 1997. Isolation, identification and cultural conditions of yeasts from traditional meju. Kor. J. Appl. Microb. Biotech. 25: 435-441
  17. Matsubara, Y., H. Kumamoto, Y. Iizuka, T. Murakami, K. Okamoto, and H. Miyakeh. 1985. Structure and hypotensive effect of flavonoid glycosides in Citrus unshiu peelings. Agric. Biol. Chem. 49: 909-913
  18. Morigiwa, A., K. Kitabatake, Y. Fujimoto, and N. Ikekawa. 1986. Angiotensin converting enzyme-inhibitory triterpenes from G. lucidum. Chem. Pharm. Bull. 34: 3025- 3028
  19. Oh, K.-S., D.-K. Na, M.-H. Kweon, and H.-C. Sung. 2003. Expression and purification of delta sleep-inducing peptide in Escherichia coli. J. Microbiol. Biotechnol. 13: 620-623
  20. Oh, K.-S., Y.-S. Park, and H.-C. Sung. 2002. Expression and purification of an ACE-inhibitory peptide multimer from synthetic DNA in Escherichia coli. J. Microbiol. Biotechnol.12: 59-64
  21. Okuda, T., T. Yoshida, and T. Hatano. 1989. Ellagitannins as active constituents of medicinal plants. Planta Medica 55:117-120
  22. Ondetti, M. A., B. Rubin, and D. W. Cushman. 1977. Design of specific inhibitors of angiotensin converting enzyme: New class of orally active antihypertensive agent. Science 196: 441-444
  23. Ondetti, M. A., B. Rubin, and D. W. Cushman. 1982. Enzyme of the rennin-angiotensin system and their inhibitors. Annu. Rev. Biochem. 51: 283-308
  24. Pal, L. V., S. R. Janet, E. L. Laura, E. S. Ralph, and E. W. Patrick. 1995. Angiotensin and bradykinin metabolism by peptidases identified in cultured human skeletal muscle myocytes and fibroblasts. J. Peptides 16: 1367-1373
  25. Rhee, K. H. 2003. Purification and identification of an antifungal agent from Streptomyces sp. KH-614 antagonistic to rice blast fungus, Pyricularia oryzae. J. Microbiol. Biotechnol. 13: 984-988
  26. Rhyu, M. R., Y. J. Nam, and H. Y. Lee. 1996. Screening of angiotensin I-converting enzyme inhibitors in cereals and legumes. Food. Biotechnol. 5: 334-337
  27. 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. Biotech. Biochem. 58: 1767-1771
  28. 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. Food. Biotechnol. 6: 122- 128
  29. Ukeda, H., H. Matsuda, H. Kuroda, K. Osajima, H. Matsufuji, and Y. Osajima. 1991. Peptides from peptic hydrolyzate sardine meat that inhibit angiotensin converting enzyme. Nippon Nogekagaku Kaishi 65: 1223-1228