Applied Microbiology and Biotechnology

, Volume 103, Issue 23–24, pp 9335–9344 | Cite as

An overview of the biological production of 1-deoxynojirimycin: current status and future perspective

  • Wenli Zhang
  • Wanmeng Mu
  • Hao WuEmail author
  • Zhiqun LiangEmail author


1-Deoxynojirimycin (DNJ), a representative iminopyranose, is widely used in anti-diabetic, antioxidant, anti-inflammatory, and anti-obesity applications. It naturally exists in plants, insects, and the culture broth of some microbes as a secondary metabolite product. However, the content of DNJ in plants and insects is relatively low, which is an obstacle to investigating DNJ in terms of structure–function relationships and restricts large-scale industrial production. With the development of micro-biotechnology, the production of DNJ during microbial fermentation has potential for industrial applications. In this review, we primarily focus on the microbial production of DNJ. The review covers sources of DNJ, determination methods, and physiological functions and applications. In a discussion of the efficient production of DNJ microorganisms, we summarize the current methods for DNJ screening and how to guide industrialized large-scale production of DNJ through fermentation regulation strategies. In addition, differences in the biosynthetic pathways of DNJ in different sources are also summarized. Finally, a comparison of DNJ content derived from different sources is discussed.


1-Deoxynojirimycin Microbial production Applications Biosynthetic pathway Regulation strategy 


Funding information

This work was financially supported by Innovation Project of Guangxi Graduate Education (YCBZ2017022), National Natural Science Foundation of China (31560448).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. Asai A, Nakagawa K, Higuchi O, Kimura T, Kojima Y, Kariya J, Miyazawa T, Oikawa S (2011) Effect of mulberry leaf extract with enriched 1-deoxynojirimycin content on postprandial glycemic control in subjects with impaired glucose metabolism. J Diabetes Invest 2(4):318–323. CrossRefGoogle Scholar
  2. Asano N (2003) Naturally occurring iminosugars and related compounds: structure, distribution, and biological activity. Curr Top Med Chem 3(5):471–484. CrossRefPubMedGoogle Scholar
  3. Asano N, Kato A, Matsui K (1996) Two subsites on the active center of pig kidney trehalase. Eur J Biochem 240(3):692–698. CrossRefPubMedGoogle Scholar
  4. Asano N, Kato A, Miyauchi M, Kizu H, Kameda Y, Watson AA, Nash RJ, Fleet GW (1998) Nitrogen-containing furanose and pyranose analogues from Hyacinthus orientalis. J Nat Prod 61(5):625–628. CrossRefPubMedGoogle Scholar
  5. Asano N, Nishida M, Miyauchi M, Ikeda K, Yamamoto M, Kizu H, Kameda Y, Watson AA, Nash RJ, Fleet GW (2000) Polyhydroxylated pyrrolidine and piperidine alkaloids from Adenophora triphylla var. japonica (Campanulaceae). Phytochemistry 31(20):379–382. CrossRefGoogle Scholar
  6. Asano N, Yamashita T, Yasuda K, Ikeda K, Kizu H, Kameda Y, Kato A, Nash RJ, Lee HS, Ryu KS (2001) Polyhydroxylated alkaloids isolated from mulberry trees (Morusalba L.) and silkworms (Bombyx mori L.). J Agric Food Chem 49(9):4208–4213. CrossRefPubMedGoogle Scholar
  7. Chan KC, Lin MC, Huang CN, Chang WC, Wang CJ (2013) Mulberry 1-deoxynojirimycin pleiotropically inhibits glucose-stimulated vascular smooth muscle cell migration by activation of AMPK/RhoB and down-regulation of FAK. J Agric Food Chem 61(41):9867–9875. CrossRefPubMedGoogle Scholar
  8. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M (2002) Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 359(9323):2072–2077. CrossRefPubMedGoogle Scholar
  9. Cho Y-S, Park Y-S, Lee J-Y, Kang K-D, Hwang K-Y, Seong S-I (2008) Hypoglycemic effect of culture broth of Bacillus subtilis S10 producing 1-deoxynojirimycin. J Korean Soc Food Sci Nutr 37(11):1401–1407. CrossRefGoogle Scholar
  10. Clark LF, Johnson JV, Horenstein NA (2011) Identification of a gene cluster that initiates azasugar biosynthesis in Bacillus amyloliquefaciens. Chembiochem 12(14):2147–2150. CrossRefPubMedGoogle Scholar
  11. Dabhi AS, Bhatt NR, Shah MJ (2013) Voglibose: an alpha glucosidase inhibitor. J Clin Diagn Res 7(12):3023–3027. CrossRefPubMedPubMedCentralGoogle Scholar
  12. Dinicolantonio JJ, Bhutani J, O'Keefe JH (2015) Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes. Open Heart 2(1):e000327. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Do HJ, Chung JH, Hwang JW, Kim OY, Lee J-Y, Shin M-J (2015) 1-Deoxynojirimycin isolated from Bacillus subtilis improves hepatic lipid metabolism and mitochondrial function in high-fat–fed mice. Food Chem Toxicol 75:1–7. CrossRefPubMedGoogle Scholar
  14. E S, Yamamoto K, Sakamoto Y, Mizowaki Y, Iwagaki Y, Kimura T, Nakagawa K, Miyazawa T, Tsuduki T (2017) Intake of mulberry 1-deoxynojirimycin prevents colorectal cancer in mice. J Clin Biochem Nutr 61(1):47–52. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Ezure Y, Maruo S, Miyazaki K, Kawamata M (1985) Moranoline (1-deoxynojirimycin) fermentation and its improvement. Agric Biol Chem 49(4):1119–1125. CrossRefGoogle Scholar
  16. Gao K, Zheng C, Wang T, Zhao H, Wang J, Wang Z, Zhai X, Jia Z, Chen J, Zhou Y (2016) 1-Deoxynojirimycin: occurrence, extraction, chemistry, oral pharmacokinetics, biological activities and in silico target fishing. Molecules 21(11):1600–1615. CrossRefPubMedCentralGoogle Scholar
  17. Goh SY, Cooper ME (2008) Clinical review: The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 93(4):1143–1152. CrossRefPubMedGoogle Scholar
  18. Hardick DJ, Hutchinson DW (1993) The biosynthesis of 1-deoxynojirimycin in Bacillus subtilis var niger. Tetrahedron 49(30):6707–6716. CrossRefGoogle Scholar
  19. Hardick DJ, Hutchinson DW, Trew SJ, Wellington EM (1992) Glucose is a precursor of 1-deoxynojirimycin and 1-deoxymannonojirimycin in Streptomyces subrutilus. Tetrahedron 48(30):6285–6296. CrossRefGoogle Scholar
  20. Hu XQ, Thakur K, Chen GH, Hu F, Zhang JG, Zhang HB, Wei ZJ (2017) Metabolic effect of 1-deoxynojirimycin from mulberry leaves on db/db diabetic mice using liquid chromatography-mass spectrometry based metabolomics. J Agric Food Chem 65(23):4658–4667. CrossRefPubMedGoogle Scholar
  21. International Diabetes Federation (2017) IDF Diabetes Atlas 8th ednGoogle Scholar
  22. Jiang PX, Mu SS, Li H, Li YH, Feng CM, Jin JM, Tang SY (2015) Design and application of a novel high-throughput screening technique for 1-deoxynojirimycin. Sci Rep 5:8563. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Kim HS, Kim YH, Hong YS, Paek NS, Lee HS, Kim TM, Kim KW, Lee JJ (1999) α-Glucosidase inhibitors from Commelina communis. Planta Med 65(5):437–439. CrossRefPubMedGoogle Scholar
  24. 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 reversed-phase high-performance liquid chromatography. J Chromatogr A 1002(1-2):93–99. CrossRefPubMedGoogle Scholar
  25. Kimura T, Nakagawa K, Saito Y, Yamagishi K, Suzuki M, Yamaki K, Shinmoto H, Miyazawa T (2004a) Determination of 1-deoxynojirimycin in mulberry leaves using hydrophilic interaction chromatography with evaporative light scattering detection. J Agric Food Chem 52(6):1415–1418. CrossRefPubMedGoogle Scholar
  26. Kimura T, Nakagawa K, Saito Y, Yamagishi K, Suzuki M, Yamaki K, Shinmoto H, Miyazawa T (2004b) Simple and rapid determination of 1-deoxynojirimycin in mulberry leaves. Biofactors 22(1-4):341–345. CrossRefPubMedGoogle Scholar
  27. Kimura T, Nakagawa K, Kubota H, Kojima Y, Goto Y, Yamagishi K, Oita S, Oikawa S, Miyazawa T (2007) Food-grade mulberry powder enriched with 1-deoxynojirimycin suppresses the elevation of postprandial blood glucose in humans. J Agric Food Chem 55(14):5869–5874. CrossRefPubMedGoogle Scholar
  28. Kojima M, Tachikake N, Kyotani Y, Konno K, Maruo S, Yamamoto M, Ezure Y (1995) Effect of dissolved oxygen and pH on moranoline (1-deoxynojirimycin) fermentation by Streptomyces lavendulae. J Ferment Bioeng 79(4):391–394. CrossRefGoogle Scholar
  29. Kojima Y, Kimura T, Nakagawa K, Asai A, Hasumi K, Oikawa S, Miyazawa T (2010) Effects of mulberry leaf extract rich in 1-deoxynojirimycin on blood lipid profiles in humans. J Clin Biochem Nutr 47(2):155–161. CrossRefPubMedPubMedCentralGoogle Scholar
  30. Kwon HJ, Chung JY, Kim JY, Kwon O (2011) Comparison of 1-deoxynojirimycin and aqueous mulberry leaf extract with emphasis on postprandial hypoglycemic effects:in vivo and invitro studies. J Agric Food Chem 59(7):3014–3019. CrossRefPubMedGoogle Scholar
  31. Lee SM (2013) 1-Deoxynojirimycin isolated from a Bacillus subtilis stimulates adiponectin and GLUT4 expressions in 3T3-L1 adipocytes. J Microbiol Biotechnol 23(5):637–643. CrossRefPubMedGoogle Scholar
  32. Li J, Liu L, Yu PP, Huang MH, Zhang YK, Chen GG, Liang ZQ (2012) Screening of α-glucosidase inhibitor-producing strain and optimization of fermentation conditions. Food Sci 33(23):249–253 (In Chinese) Google Scholar
  33. Li YG, Ji DF, Zhong S, Lin TB, Lv ZQ, Hu GY, Wang X (2013) 1-Deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism in streptozotocin-induced diabetic mice. Sci Rep 3:1377. CrossRefPubMedPubMedCentralGoogle Scholar
  34. Liu SX, Hua JL, Li HL (2011) Study on ultrasonic extraction of 1-deoxynojirimycin (DNJ) and polysacchrides from mulberry leaves. Adv Mater Res 236-238:2759–2764. CrossRefGoogle Scholar
  35. Maruo S, Yamashita H, Miyazaki K, Yamamoto H, Kyotani Y, Ogawa H, Kojima M, Ezure Y (1992) A novel and efficient method for enzymatic synthesis of high purity maltose using moranoline (1-deoxynojirimycin). Biosci Biotechnol Biochem 56(9):1406–1409. CrossRefPubMedGoogle Scholar
  36. Maruo S, Yamamoto H, Toda M, Tachikake N, Kojima M, Ezure Y (1993) Enzymatic synthesis of high purity maltotetraose using moranoline(1-deoxynojirimycin). Biosci Biotechnol Biochem 57(3):499–501. CrossRefPubMedGoogle Scholar
  37. Nakagawa K, Kubota H, Kimura T, Yamashita S, Tsuzuki T, Oikawa S, Miyazawa T (2007) Occurrence of orally administered mulberry 1-deoxynojirimycin in rat plasma. J Agric Food Chem 55(22):8928–8933. CrossRefPubMedGoogle Scholar
  38. Nakagawa K, Ogawa K, Higuchi O, Kimura T, Miyazawa T, Hori M (2010) Determination of iminosugars in mulberry leaves and silkworms using hydrophilic interaction chromatography-tandem mass spectrometry. Anal Biochem 404(2):217–222. CrossRefPubMedGoogle Scholar
  39. Niwa T, Inouye S, Tsuruoka T, Koaze Y, Niida T (1970) “Nojirimycin” as a potent inhibitor of glucosidase. Agric Biol Chem 34(6):966–968. CrossRefGoogle Scholar
  40. Nuengchamnong N, Ingkaninan K, Kaewruang W, Wongareonwanakij S, Hongthongdaeng B (2007) Quantitative determination of 1-deoxynojirimycin in mulberry leaves using liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal 44(4):853–858. CrossRefPubMedGoogle Scholar
  41. Onose S, Ikeda R, Nakagawa K, Kimura T, Yamagishi K, Higuchi O, Miyazawa T (2013) Production of the alpha-glycosidase inhibitor 1-deoxynojirimycin from Bacillus species. Food Chem 138(1):516–523. CrossRefPubMedGoogle Scholar
  42. 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(4):262–266 Google Scholar
  43. Papandreou MJ, Barbouche R, Guieu R, Kieny MP, Fenouillet E (2002) The alpha-glucosidase inhibitor 1-deoxynojirimycin blocks human immunodeficiency virus envelope glycoprotein-mediated membrane fusion at the CXCR4 binding step. Mol Pharmacol 61(1):186–193. CrossRefPubMedGoogle Scholar
  44. Park E, Lee S-M, Lee J, Kim J-H (2013) Anti-inflammatory activity of mulberry leaf extract through inhibition of NF-κB. J Funct Foods 5(1):178–186. CrossRefGoogle Scholar
  45. Rayamajhi V, Dhakal D, Chaudhary AK, Sohng JK (2018) Improved production of 1-deoxynojirymicin in Escherichia coli through metabolic engineering. World J Microbiol Biotechnol 34(6):77–11. CrossRefPubMedGoogle Scholar
  46. Scott LJ, Spencer CM (2000) Miglitol: a review of its therapeutic potential in type 2 diabetes mellitus. Drugs 59(3):521–549. CrossRefPubMedGoogle Scholar
  47. Shibano M, Fujimoto Y, Kushino K, Kusano G, Baba K (2004) Biosynthesis of 1-deoxynojirimycin in Commelina communis: a difference between the microorganisms and plants. Phytochemistry 65(19):2661–2665. CrossRefPubMedGoogle Scholar
  48. Shibano M, Kakutani K, Taniguchi M, Yasuda M, Baba K (2008) Antioxidant constituents in the dayflower (Commelina communis L.) and their α-glucosidase-inhibitory activity. J Nat Med 62(3):349–353. CrossRefPubMedGoogle Scholar
  49. Stein DC, Kopec L, Yasbin R, Young F (1984) Characterization of Bacillus subtilis DSM704 and its production of 1-deoxynojirimycin. Appl Environ Microbiol 48(2):280–284 PubMedPubMedCentralGoogle Scholar
  50. Tao Y, Zhang Y, Cheng Y, Wang Y (2013) Rapid screening and identification ofα-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. Biomed Chromatogr 27(2):148–155. CrossRefPubMedGoogle Scholar
  51. Thakur K, Zhang YY, Mocan A, Zhang F, Zhang JG, Wei Z (2019) 1-Deoxynojirimycin, its potential for management of non-communicable metabolic diseases. Trends Food Sci Technol 89:88–99. CrossRefGoogle Scholar
  52. Tsuduki T, Kikuchi I, Kimura T, Nakagawa K, Miyazawa T (2013) Intake of mulberry 1-deoxynojirimycin prevents diet-induced obesity through increases in adiponectin in mice. Food Chem 139(1-4):16–23. CrossRefPubMedGoogle Scholar
  53. Vichasilp C, Nakagawa K, Sookwong P, Suzuki Y, Kimura F, Higuchi O, Miyazawa T (2009) Optimization of 1-deoxynojirimycin extraction from mulberry leaves by using response surface methodology. Biosci Biotechnol Biochem 73(12):2684–2689. CrossRefPubMedGoogle Scholar
  54. Wang T, Li CQ, Zhang H, Li JW (2014) Response surface optimized extraction of 1-deoxynojirimycin from mulberry leaves (Morus alba L.) and preparative separation with resins. Molecules 19(6):7040–7056. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Wang D, Zhao L, Wang D, Liu J, Yu X, Wei Y, Ouyang Z (2018) Transcriptome analysis and identification of key genes involved in 1-deoxynojirimycin biosynthesis of mulberry (Morus alba L.). Peer J 6:e5443. CrossRefPubMedGoogle Scholar
  56. Wei ZJ, Zhou LC, Chen H, Chen GH (2011) Optimization of the fermentation conditions for 1-deoxynojirimycin production by Streptomyces lavendulae applying the response surface methodology. Int J Food Eng 7(3):1–10. CrossRefGoogle Scholar
  57. Wu H, Zeng W, Chen L, Yu B, Guo Y, Chen GG, Liang ZQ (2018) Integrated multi-spectroscopic and molecular docking techniques to probe the interaction mechanism between maltase and 1-deoxynojirimycin, an α-glucosidase inhibitor. Int J Biol Macromol 114:1194–1202. CrossRefPubMedGoogle Scholar
  58. Wu H, Guo Y, Chen L, Chen GG, Liang ZQ (2019a) A novel strategy to regulate 1-deoxynojirimycin production based on its biosynthetic pathway in Streptomyces lavendulae. Front Microbiol 10:1968. CrossRefPubMedPubMedCentralGoogle Scholar
  59. Wu H, Zeng W, Chen GG, Guo Y, Yao CZ, Li J, Liang ZQ (2019b) Spectroscopic techniques investigation on the interaction of glucoamylase with 1-deoxynojirimycin: Mechanistic and conformational study. Spectrochim Acta A 206:613–621. CrossRefGoogle Scholar
  60. Xu B, Zhang DY, Liu ZY, Zhang Y, Liu L, Li L, Liu CC, Wu GH (2015) Rapid determination of 1-deoxynojirimycin in Morus alba L. leaves by direct analysis in real time (DART) mass spectrometry. J Pharm Biomed Anal 114:447–454. CrossRefPubMedGoogle Scholar
  61. Yagi M, Kouno T, Aoyagi Y, Murai H (1976) The structure of moranoline, a piperidine alkaloid from Morus species. J Agric Chem Soc Jpn 50(11):571–572. CrossRefGoogle Scholar
  62. Yamagishi K, Onose S, Takasu S, Ito J, Ikeda R, Kimura T, Nakagawa K, Miyazawa T (2017) Lactose increases the production of 1-deoxynojirimycin in Bacillus amyloliquefaciens. Food Sci Technol Res 23(2):349–353. CrossRefGoogle Scholar
  63. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kadowaki T (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 8(8):941–946. CrossRefGoogle Scholar
  64. Yoo Y, Seo DH, Lee H, Cho ES, Song NE, Nam TG, Nam YD, Seo MJ (2019) Inhibitory effect of Bacillus velezensis on biofilm formation by Streptococcus mutans. J Biotechnol 298:57–63. CrossRefPubMedGoogle Scholar
  65. Yoshihashi T, Do HTT, Tungtrakul P, Boonbumrung S, Yamaki K (2010) Simple, selective, and rapid quantification of 1-deoxynojirimycin in mulberry leaf products by high-performance anion-exchange chromatography with pulsed amperometric detection. J Food Sci 75(3):246–250. CrossRefGoogle Scholar
  66. Zhou LC, Wei ZJ, Zhang HX, Jiang L (2009) Screening and identification of 1-deoxynojirimycin-producing bacteria strain. Food Sci 30(23):361–364 (in Chinese) Google Scholar
  67. Zhu YP, Li XT, Teng C, Sun BG (2013) Enhanced production of α-glucosidase inhibitor by a newly isolated strain of Bacillus subtilis B2 using response surface methodology. Food Bioprod Process 91(3):264–270. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Food Science and TechnologyJiangnan UniversityWuxiChina
  2. 2.International Joint Laboratory on Food SafetyJiangnan UniversityWuxiChina
  3. 3.State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and TechnologyGuangxi UniversityNanningChina

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