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Fermentation Microbiology (FM)  |  Fermentation Technology

Microbiol. Biotechnol. Lett. 2021; 49(4): 566-575

https://doi.org/10.48022/mbl.2111.11008

Received: November 15, 2021; Revised: December 8, 2021; Accepted: December 10, 2021

Production of α-Glucosidase Inhibitor and 1-Deoxynojirimycin by Bacillus subtilis MORI

Young Shik Park, Jae Yeon Lee, Kyo Yeol Hwang, and Keun Kim*

Department of Biotechnology and Biomarketing, The University of Suwon, Hwaseong 18323, Republic of Korea

Correspondence to :
Keun Kim,      kkim@suwon.ac.kr

Galactose and soybean meal were selected as the best carbon and nitrogen sources, repectively, for the efficient production of α-glucosidase inhibitor (AGI) and 1-deoxynojirimycin (DNJ) by a newly isolated Bacillus subtilis MORI. The optimal concentrations of the galactose and soybean meal for the production of AGI and DNJ were investigated by response surface methodology. For the production of AGI, the optimal galactose and soybean meal concentrations were 4.3% (w/v) and 3.2% (w/v), respectively, and for DNJ, 4.5% (w/v) and 3.0% (w/v), respectively. The nearly identical optimal concentrations of galactose and soybean meal for the production of both AGI and DNJ indicated a close correlation between the production of AGI and DNJ. The maximum production of AGI (50,880 GIU/ml) and DNJ (824 μg/ml) obtained from the statistically optimized medium in a jar fermenter was 2.33 and 2.38-fold, respectively, higher than those (21,798 GIU/ml and 346 μg/ml, respectively) of the pre-optimized medium. The production of both AGI and DNJ was greatly increased by jar fermentation (AGI of 38,524 GIU/ml and DNJ of 491 μg/ml) compared with flask fermentation.

Keywords: &alpha,-Glucosidase inhibitor, 1-deoxynojirimycin, production, Bacillus subtilis MORI, response surface methodology

Graphical Abstract


  1. DeFronzo RA. 2004. Pathogenesis of type 2 diabetes mellitus. Med. Clin. North Am. 88: 787-835.
    Pubmed
  2. Frandsen TP, Svensson B. 1998. Plant α-glucosidases of glycoside hydrolase family 31. Molecular properties, substrate specificity, reaction mechanism, and comparison with family members of different origin. Plant Mol. Biol. 37: 1-13.
  3. Alain DB. 1998. Postprandial hyperglycaemia and α-glucosidase inhibitors. Diabetes Res. Clin. Pract. 40: 51-55.
  4. Floris AV, Peter LL, Reinier PA, Eloy HV, Guy ER, Chris VW. 2005. αGlucosidase inhibitors for patients with type 2 diabetes. Diabetic Care 28: 154-162.
  5. Holman RR. 1998. Assessing the potential for α-glucosidase inhibitors in prediabetic states. Diabetes Res. Clin. Pract. 40: 21-25.
  6. Patricia MH, Steven RH, Jennifer AW, Bryan WW. 2005. Effects of a medical food containing an herbal α-glucosidase on postprandial glycaemia and insulinemia in healthy adults. J. Am. Diet Assoc. 105: 65-71.
    Pubmed
  7. Clissold SP, Edwards C. 1998. Acarbose, a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 35: 214-243.
    Pubmed
  8. Toeller M. 1994. α-Glucosidase inhibitors in diabetes: efficacy in NIDDM subjects. Eur. J. Clin. Invest. 24: 31-35.
    Pubmed
  9. Murai A, Iwamura K, Takada M, Ogawa K, Usui T, Okumura J. 2002. Control of postprandial hyperglycaemia by galactosyl maltobionolactone and its novel anti-amylase effect in mice. Life Sci. 71: 1405-1415.
  10. Chen J, Cheng YQ, Yamaki K, Li LT. 2007. Anti-α-glucosidase activity of Chinese traditionally fermented soybean (douche). Food Chem. 103: 1091-1096.
  11. Kwon DY, Daily JW 3rd, Kim HJ, Park S. 2010. Antidiabetic effects of fermented soybean products on type 2 diabetes. Nutr. Res. 30:1-13.
    Pubmed
  12. Yoshikawa M, Morikawa T, Matsuda H, Tannbe G, Muraoka O. 2002. Absolute stereostructure of potent α-glucosidase inhibitor, salacinol, with unique thiosugar sulfonium sulfate inner salt structure from Salacia reticulata. Bioorg. Med. Chem. 10: 15471554.
  13. Liu Y, Ma L, Chen WH, Wang B, Xu ZL. 2007. Synthesis of xanthone derivatives with extended π-sytems as α-glucosidase inhibitors:Insight into the probable binding mode. Bioorg. Med. Chem. 15:2810-2814.
    Pubmed
  14. Muraoka O, Yoshikai K, Takahashi H, Minematsu T, Lu G, Tanabe G, et al. 2006. Synthesis and biological evaluation of deoxy salacinols, the role of polar substituents in the side chain on the α-glucosidase inhibitory activity. Bioorg. Med. Chem. 14: 500-509.
    Pubmed
  15. Iwasa R, Yamagami H, Shibata M. 1970. Studies on validamycins, new antibiotic I. Streptomyces hygroscopicus var. limoneus. validamycin producing organiam. J. Antibiotechnol. 23: 595-602.
    Pubmed
  16. Schmidt DD, Frommer W, Junge B, Müller L, Wingender W, Truscheit E, et al. 1977. α-glucosidase inhibitors, new complex oligosaccharides of microbial origin. Naturwissenschaften 64:535-536.
    Pubmed
  17. Kameda Y, Asano N, Teranishi M, Natsui K. 1980. New cyclitols, degradation of validamycin A by Flavobacterium saccharophilum. J. Antibiot.(Tokyo) 33: 1573-1574.
    Pubmed
  18. Zhu YP, Fan JF, Cheng YQ, Li LT. 2008 Improvement of the antioxidant activity of Chinese traditional fermented okara (Meitauza) using Bacillus subtilis B2. Food Control 19: 654-661.
  19. Zhu YP, Yin LJ, Cheng YQ, Yamaki K, Mori Y, Su YC, et al. 2008. Effects of sources of carbon and nitrogen on production of αglucosidase inhibitor by a newly isolated of Bacillus subtilis B2. Food Chem. 109: 737-742.
    Pubmed
  20. Romaniouk AV, Silva A, Feng J, Vijay IK. 2004. Synthesis of a novel photoaffinity derivative of 1-deoxynojirimycin for active sitedirected labeling of glucosidase I. Glycobiol. 14: 301-310.
    Pubmed
  21. Yagi M, Kono T, Aoyagi Y, Murai H. 1976. The structure of moraoline, a piperidine alkaloid from Morus species. Nippon Nougei kagaku kaishi 50: 571-572.
  22. Kimura T, Nakagawa K, Saito Y, Yamagishi K, Suzuki M, Yamaki K, et al. 2004. Simple and rapid determination of 1-deoxynojirimycin in mulberry leaves. Biofactors 22: 341-345.
    Pubmed
  23. Stein DC, Kopec LK, Yasbin RE, Young FE. 1984. Characterization of Bacillus subtilis DSM704 and its production of 1-deoxynojirimycin. Appl. Environ. Microbiol. 8: 280-284.
    Pubmed KoreaMed
  24. Schmidt DD, Frommer W, Müller L, Truscheit E. 1979. Glucosidase inhibitiors from Bacilli. Naturwissenschaften. 66: 584-585.
    Pubmed
  25. Murao S, Miyata S. 1980. Isolation and characterization of a new trehalase inhibitor, S-GI. Agric. Biol. Chem. 44: 219-221.
  26. Ezure Y, Marue S, Miyazaki K, Kawamata M. 1985. Moranoline(1deoxynojirimycin) fermentation and its improvement. Agric. Biol. Chem. 49: 1119-1125.
  27. Chen HM, Yan XJ, Lin W, Zheng L, Zhang WW. 2004. A new method for screening alpha-glucosidase inhibitors and application to marine microorganisms. Pharm. Biol. 42: 416-421.
  28. Paek NS, Kang DJ, Choi YJ, Lee JJ, Kim TH, Kim KW. 1997. Production of 1-deoxynojirimycin by Streptomyces sp. SID9135. J. Microbiol. Biotechnol. 7: 262-266.
  29. Haaland PD. 1989. Experimental design in biotechnology. New York: Dekker.
  30. Box GEP, Wilson KB. 1951. On the experimental attainment of optimum condition. J. Roy. Stat. Soc. B. 13: 1-45.
  31. Lim JS, Park MC, Lee JH, Park SW, Kim SW. 2005. Optimization of culture medium and conditions for neofructooligosaccharides production by Penicillium citrinum. Eur. Food Res. Technol. 221:639-644.
  32. Vichasilp C, Nakagawa K, Sookqong P, Suzuki Y, Kimura F, Higuchi O, et al. 2009. Optimization of 1-deoxynojirimycin extraction from mulberry leaves by using response surface methodology. Biosci. Biotechnol. Biochem. 73: 2684-2689.
    Pubmed
  33. Kalil SJ, Maugeri F, Rodrigues MI. 2000. Response surface analysis and simulation as a tool for bioprocess design and optimization. Process Biochem. 35: 539-550.
  34. Kim HS, Lee JY, Hwang KY, Cho YS, Park YS, Kang KD, et al. 2011. Isolation and identification of a Bacillus sp. producing α-glucosidase inhibitor 1-deoxynojirimycin. Korean J. Microbiol. Biotechnol. 39:49-55.
  35. Montgomery DC. 1991. Design and analysis of experiments. 3rd Ed. NY: Wiley.
  36. Matsui T, Ueda T, Oki T, Sugita K, Terahara N, Matsumoto K. 2001. α-glucosidase inhibitory action of natural acylated anthocyanins. 1. Survey of natural pigments with potent inhibitory activity. J. Agric. Food Chem. 49: 1948-1951.
    Pubmed
  37. Kim JW, Kim SU, Lee HS, Kim I, Ahn MY, Ryu KS. 2003. Determination of 1-deoxynojirimycin in Morus alba L. leaves by derivatization with 9-fluorenylmethyl chloroformate followed by reversedphase high-performance liquid chromatography. J. Chromatogr. A. 1002: 93-99.
  38. Kada S, Yabusaki M, Kaga T, Ashida H, Yoshida K. 2008. Identification of two major ammonia-releasing reactions involved in secondary fermentation. Biosci. Biotechnol. Biochem. 72: 1869-1876.
    Pubmed
  39. Kharel MK, Lee HC, Sohng JK, Liou K. 2002. Statistical optimization of medium components for the improved production of cystocin by Streptomyces sp. GCA0001. J. Ind. Eng. Chem. 8: 427431.
  40. Yatsunami K, Ichida M, Onodera S. 2008. The relationship between 1-deoxynojirimycin content and α-glucosidase inhibitory activity in leaves of 276 mulberry cultivars (Morus spp.) in Kyoto, Japan. J. Nat. Med. 62: 63-66.
    Pubmed
  41. Zhu YP, Yamaki K, Yoshihashi T, Kameyama MO, Li XT, Cheng YQ, et al. 2010. Purification and identification of 1-deoxynojirimycin (DNJ) in okara fermented by Bacillus subtilis B2 from Chinese traditional food (Meitaoza). J. Agric. Food Chem. 58: 4097-4103.
    Pubmed
  42. Pavlova K, Grigorova D. 1999. Production and properties of exopolysaccharide by Rhodotorula acheniorum MC. Food Res. Int. 32:473-477.

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