(Bacillus subtilis) (Bacillus natto spore)

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1 (Bacillus subtilis) (Bacillus natto spore) 2000 B 1 B 2 E K B1 B2 K2 kcal g g g g U/g

2 E 1995 Angiotension K K SOD K 2 Catalase 1967 KMD B (LDL) : 1986 K 2 O-157 (Helicobacter pylori)

3 angiotensin converting enzyme (ACE) K NHK 4,5 (nattokinase) DNA ph4 ~12 ph7~9 Nattokinase Enzyme Ralph E. Holsworth: Nattokinase and Cardiovascular Health, (urokinase) (FU) (thiol reductant) 6,7 FDA Tulane , ~60 B 6 E K

4 (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,

5 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

6 ( ) ( ) (2005) (nutraceuticals) Nutrition Pharmaceutical Nutraceutical Science Safety LDL

7 R(peptides) (glycopeptides) 6 -O-succinyl 19 PPQ (pyrroloquinoline quinone) (Bifidus) (natto micronutrients) (amylase)(protease) (natural antioxidative factors) 20 Euromonitor ( ) 1. Zuber, P., M. M. Nakano, and M. A. Marahiel Peptide antibiotics, p 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: 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: 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: 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:

8 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): 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: 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): 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: 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): 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: 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: 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): Ashiuchi, M., C. Nawa, T. Kamei, J. J. Song, S. P. Hong, M. H. Sung, K. Soda, and H. Misono Physiological and biochemical characteristics of poly-γ-glutamate synthetase complex of Bacillus subtilis. Eur. J. Biochem. 268: Ashiuchi, M., and H. Misono. Biochemistry and molecular genetics of poly-γ-glutamate synthesis. Appl. Microbiol. Biotechnol, 2002; 59: 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: 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: 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): 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): 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):

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