(Bacillus subtilis) (Bacillus natto spore)

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(Bacillus subtilis) (Bacillus natto spore) 2000 B 1 B 2 E K 2 2300 754 1286 B1 B2 K2 kcal g g g g U/g 180 16 9 7.6 2.1 70 2 1 570 0.22 0.09 41 200 16.5 10 9.8 2.3 90 3.3 2 660 0.07 0.56 870 500 2005 45

1600 100 2 21 1982 E 1995 Angiotension K K SOD K 2 Catalase 1967 KMD1126 1987 B2 1996 0-157 0-157 1 0-157 (LDL) : 1986 K 2 O-157 (Helicobacter pylori) 3 46 2005

angiotensin converting enzyme (ACE) K2 3 200 NHK 4,5 (nattokinase) 12 50 100 1. DNA 275 27728 2. 8.6 0.3 3. ph4 ~12 ph7~9 Nattokinase Enzyme Ralph E. Holsworth: Nattokinase and Cardiovascular Health, http://www.nutrimart.com/pdf/nattoreport.pdf, 2002 (urokinase) 20 1 1600 (FU) (thiol reductant) 6,7 FDA Tulane 25 74 1,100 14 20 50~60 B 6 E K 2 8 2005 47

(reactive oxygen species, ROS) 9 KMD1126 KMD1126 Ehrlich ascites carcinoma (interferon) 30 (edamame therapy) (purine) K 2 (osteoclast calcium) Gla 10 K 2 (coagulation) K 2 K 2 K 2 K 2 11,12 48 2005

13 (probiotics) (endospore) (γ-poly-glutamic acid, γ- PGA) 14,15 - (urokinase) (tissue plasminogen activator, t-pa) (ACE inhibitor) K 2 17,18,19 (100 C) (vegetative cells) D 2005 49

2005 50 2002 (2000-2002) (2002-2004) (2005) (nutraceuticals) Nutrition Pharmaceutical Nutraceutical Science Safety LDL

R(peptides) (glycopeptides) 6 -O-succinyl 19 PPQ (pyrroloquinoline quinone) (Bifidus) (natto micronutrients) (amylase)(protease) (natural antioxidative factors) 20 Euromonitor 13.5 2006 600 40 30 (1998-2004) 1. Zuber, P., M. M. Nakano, and M. A. Marahiel. 1993. Peptide antibiotics, p. 897-916. In A. L. Sonenshein, J. A. Hoch, and R. Losick (ed.), Bacillus subtilis and other gram-positive bacteria: biochemistry, physiology, and molecular genetics. American Society for Microbiology, Washington, D.C. 2. T. Yamashita, E. Oda a, J.C. Giddings, J. Yamamoto: The effect of dietary Bacillus natto productive protein on in vivo endogenous thrombolysis, Pathophysiology of Haemostasis and Thrombosis 2003; 33:138-143. 3. Kudva, I. T., P. S. Evans, N. T. Perna, T. J. Barrett, F. M. Ausubel, F. R. Blattner, and S. B. Calderwood. Strains of Escherichia coli O157:H7 differ primarily by insertions or deletions, not single-nucleotide polymorphisms. J. Bacteriol. 2002; 184:1873-1879. 4. Fujita M, Hong K, Ito Y, Fujii R, Kariya K, Nishimuro S: Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat. Biol Pharm Bull 1995; 18:1387-1391. 5. Kim W, Choi K, Kim Y, Park H, Choi J, Lee Y, Oh H, Kwon I, Lee S: Purification and characterization of a fibrinolytic enzyme produced from Bacillus sp. strain CK 11-4 screened from Chungkook-Jang. Appl Environ Microbiol 1996; 62: 2482-2488. 2005 51

6. Yamamoto, K. et al. Plasminogen activator inhibitor-1 is a major stress-regulated gene: implications for stress-induced thrombosis in aged individuals. Proceedings of the National Academy of Sciences. 2002; 99(2): 890-895. 7. Urano T, Ihara H, Umemura K, Suzuki Y, Oike M, Akita S, Tsukamoto Y, Suzuki I, Takada A: The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis cleaves and inactivates plasminogen activator inhibitor type 1. J Biol. Chem. 2001; 276:24690-24696. 8. Pesce, Noel ; Eyster, Kathleen M.; Williams, John L. ; Wixon, Regina ; Wang, Chunyang ; Martin, Doug S.: Effect of Genistein on Cardiovascular Responses to Angiotensin II in Conscious Unrestrained Rats, Journal of Cardiovascular Pharmacology. 2000; 36(6): 806-809. 9. Iwai K, Nakaya N, Kawasaki Y, Matsue H: Antioxidative functions of natto, a kind of fermented soybeans: Effect on LDL oxidation and lipid metabolism in cholesterol-fed rats. J Agric Food Chem 2002; 50:3597-3601. 10. Kaneki M, Hedges SJ, Hosoi T, et al. Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition 2001 Apr; 17(4): 315-21. 11. Tsukamoto Y, Ichise H, Kakuda H, Yamaguchi M: Intake of fermented soybean (natto) increases circulating vitamin K 2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals. J Bone Miner Metab 2000; 18/4: 216-222. 12. Katsuyama H, Ideguchi S, Fukunaga M, Saijoh K, Sunami S: Usual dietary intake of fermented soybeans (Natto) is associated with bone mineral density in premenopausal women. J Nutr Sci Vitaminol (Tokyo) 2002; 48/3:207-215. 13. Tomohiro Hosoi, Akio Ametani, Kan Kiuchi, and Shuichi Kaminogawa: Improved growth and viability of lactobacilli in the presence of Bacillus subtilis (natto), catalase, or subtilisin, 2000: Can. J. Microbiol./Rev. can. Microbiol. 46(10): 892-897. 14. Ashiuchi, M., C. Nawa, T. Kamei, J. J. Song, S. P. Hong, M. H. Sung, K. Soda, and H. Misono. 2001. Physiological and biochemical characteristics of poly-γ-glutamate synthetase complex of Bacillus subtilis. Eur. J. Biochem. 268:5321-5328. 15. Ashiuchi, M., and H. Misono. Biochemistry and molecular genetics of poly-γ-glutamate synthesis. Appl. Microbiol. Biotechnol, 2002; 59:9-14. 16. Liu BY, Song HY: Molecular cloning and expression of nattokinase gene in Bacillus subtilis. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) 2002; 34: 338-340. 17. Chang CT, Fan MH, Kuo FC, Sung HY: Potent fibrinolytic enzyme from a mutant of Bacillus subtilis IMR-NK1. J Agric Food Chem 2000; 48:3210-3216. 18. Yamaguchi M, Ma Z J. Inhibitory effect of menaquinone-7 (vitamin K 2 ) on osteoclast-like cell formation and osteoclastic bone resorption in rat bone tissues in vitro. Mol Cell Biochem 2001; 228(1-2): 39-47 19. Toda T, Uesugi T, Hirai K, Nukaya H, Tsuji K, Ishida H. New 6-O-acyl isoflavone glycosides from soybeans fermented with Bacillus subtilis (natto). I. 6-O-succinylated isoflavone glycosides and their preventive effects on bone loss in ovariectomized rats fed a calcium-deficient diet. Biol Pharm Bull 1999; 22(11): 1193-2011. 20. Mentor-Marcel R, Lamartiniere CA, Eltoum IA, Greenberg NM, Elgavish A. Dietary genistein improves survival and reduces expression of osteopontin in the prostate of transgenic mice with prostatic adenocarcinoma (TRAMP). 2005: J Nutr; 135(5): 989-95. 52 2005