1-Deoxynojirimycin (DNJ or 1-DNJ), also called duvoglustat or moranolin,[1] is an alpha-glucosidase inhibitor, most commonly found in mulberry leaves. Although it can be obtained in small quantities by brewing an herbal tea from mulberry leaves, interest in commercial production has led to research on developing mulberry tea higher in DNJ,[2] and on alternate routes of production, such as via Bacillus species.[3]
1-Deoxynojirimycin is a polyhydroxylated piperidine alkaloid produced from D-Glucose in various plants, such as Commelina communis, and in the Streptomyces and Bacillus bacteria.[4][5] High quantities of this azasugar are produced in Bacillus subtilis, a process initiated by a TYB gene cluster composed of gabT1 (aminotransferase), yktc1 (phosphatase), and gutB1 (oxidoreductase).[6][7]
In Bacillus subtilis, D-glucose first undergoes glycolysis, opening the 6 member ring and producing fructose-6-phosphate.[8] GabT1 catalyzes transamination at the C2 position, followed by a dephosphorylation by the Yktc1 enzyme,[7] resulting in 2-amino-2-deoxy-D-mannitol (ADM), an essential precursor.[8] Regio-selective oxidation by GutB1[7] occurs at the exposed C6 hydroxyl of ADM, pushing a C2-N-C6 cyclization of the resulting 6-oxo intermediate,[9] creating Manojirimycin (MJ). Epimerization of MJ at the C2 position yields the nojirimycin isomer. Nojirimycin is then dehydrated (loss of -OH at C1 position), along with reduction of the imine moiety.[9] This results in the product 1-DNJ.[8]
Biosynthesis of 1-deoxynojirimycin in Bacillus subtilis
Pathway variationsedit
In the Streptomyces subrutilus species, a secondary pathway branching from the manojirimycin precursor results in 1-deoxymanojirimycin via dehydration and reduction of the isomer. However, Bacillus subtilis does not produce 1-deoxymanojirimycin despite the presence of the manojirimycin precursor.[4]
Azasugar biosynthesis in Commelina communis involves C1-C5 cyclisation of the original D-glucose precursor without the subsequent inversion.[4][9]
^Chaluntorn Vichasilp; et al. (2012). "Development of high 1-deoxynojirimycin (DNJ) content mulberry tea and use of response surface methodology to optimize tea-making conditions for highest DNJ extraction". LWT - Food Science and Technology. 45 (2): 226–232. doi:10.1016/j.lwt.2011.09.008.
^Onose, S; Ikeda, R; Nakagawa, K; Kimura, T; Yamagishi, K; Higuchi, O; Miyazawa, T (2013). "Production of the α-glycosidase inhibitor 1-deoxynojirimycin from Bacillus species". Food Chemistry. 138 (1): 516–23. doi:10.1016/j.foodchem.2012.11.012. PMID 23265519.
^ abcGomollon-Bel, Fernando; Delso, Ignacio; Tejero, Tomas; Merino, Pedro (2014-11-12). "Biosynthetic Pathways to Glycosidase Inhibitors". Current Chemical Biology. 8 (1): 10–16. doi:10.2174/221279680801141112094818. hdl:10261/122571. ISSN 2212-7968.
^Kang, Kyung-Don; Cho, Yong Seok; Song, Ji Hye; Park, Young Shik; Lee, Jae Yeon; Hwang, Kyo Yeol; Rhee, Sang Ki; Chung, Ji Hyung; Kwon, Ohsuk (June 2011). "Identification of the genes involved in 1-deoxynojirimycin synthesis in Bacillus subtilis MORI 3K-85". The Journal of Microbiology. 49 (3): 431–440. doi:10.1007/s12275-011-1238-3. ISSN 1225-8873. PMID 21717329. S2CID 24841974.
^Kang, Kyung-Don; Cho, Yong Seok; Song, Ji Hye; Park, Young Shik; Lee, Jae Yeon; Hwang, Kyo Yeol; Rhee, Sang Ki; Chung, Ji Hyung; Kwon, Ohsuk (June 2011). "Identification of the genes involved in 1-deoxynojirimycin synthesis in Bacillus subtilis MORI 3K-85". The Journal of Microbiology. 49 (3): 431–440. doi:10.1007/s12275-011-1238-3. ISSN 1225-8873. PMID 21717329. S2CID 24841974.
^ abcClark, Lorraine F.; Johnson, Jodie V.; Horenstein, Nicole A. (2011-07-22). "Identification of a Gene Cluster that Initiates Azasugar Biosynthesis in Bacillus amyloliquefaciens". ChemBioChem. 12 (14): 2147–2150. doi:10.1002/cbic.201100347. ISSN 1439-4227. PMID 21786380. S2CID 32186936.
^ abcJiang, Peixia; Mu, Shanshan; Li, Heng; Li, Youhai; Feng, Congmin; Jin, Jian-Ming; Tang, Shuang-Yan (2015-02-24). "Design and Application of a Novel High-throughput Screening Technique for 1-Deoxynojirimycin". Scientific Reports. 5 (1): 8563. Bibcode:2015NatSR...5E8563J. doi:10.1038/srep08563. ISSN 2045-2322. PMC4338435. PMID 25708517.
deoxynojirimycin, also, called, duvoglustat, moranolin, alpha, glucosidase, inhibitor, most, commonly, found, mulberry, leaves, although, obtained, small, quantities, brewing, herbal, from, mulberry, leaves, interest, commercial, production, research, developi. 1 Deoxynojirimycin DNJ or 1 DNJ also called duvoglustat or moranolin 1 is an alpha glucosidase inhibitor most commonly found in mulberry leaves Although it can be obtained in small quantities by brewing an herbal tea from mulberry leaves interest in commercial production has led to research on developing mulberry tea higher in DNJ 2 and on alternate routes of production such as via Bacillus species 3 1 Deoxynojirimycin Names Preferred IUPAC name 2R 3R 4R 5S 2 Hydroxymethyl piperidine 3 4 5 triol Identifiers CAS Number 19130 96 2 Y 3D model JSmol Interactive image ChEBI CHEBI 44369 ChemSpider 27360 ECHA InfoCard 100 119 812 IUPHAR BPS 4642 KEGG D09605 PubChem CID 29435 UNII FZ56898FLE Y CompTox Dashboard EPA DTXSID70172647 InChI InChI 1S C6H13NO4 c8 2 3 5 10 6 11 4 9 1 7 3 h3 11H 1 2H2 t3 4 5 6 m1 s1Key LXBIFEVIBLOUGU JGWLITMVSA N SMILES C1 C H C H C H C H N1 CO O O O Properties Chemical formula C 6H 13N O 4 Molar mass 163 173 g mol 1 Melting point 195 C 383 F 468 K Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Infobox references Contents 1 Biosynthesis 1 1 Pathway variations 2 See also 3 ReferencesBiosynthesis edit1 Deoxynojirimycin is a polyhydroxylated piperidine alkaloid produced from D Glucose in various plants such as Commelina communis and in the Streptomyces and Bacillus bacteria 4 5 High quantities of this azasugar are produced in Bacillus subtilis a process initiated by a TYB gene cluster composed of gabT1 aminotransferase yktc1 phosphatase and gutB1 oxidoreductase 6 7 In Bacillus subtilis D glucose first undergoes glycolysis opening the 6 member ring and producing fructose 6 phosphate 8 GabT1 catalyzes transamination at the C2 position followed by a dephosphorylation by the Yktc1 enzyme 7 resulting in 2 amino 2 deoxy D mannitol ADM an essential precursor 8 Regio selective oxidation by GutB1 7 occurs at the exposed C6 hydroxyl of ADM pushing a C2 N C6 cyclization of the resulting 6 oxo intermediate 9 creating Manojirimycin MJ Epimerization of MJ at the C2 position yields the nojirimycin isomer Nojirimycin is then dehydrated loss of OH at C1 position along with reduction of the imine moiety 9 This results in the product 1 DNJ 8 nbsp Biosynthesis of 1 deoxynojirimycin in Bacillus subtilis Pathway variations edit In the Streptomyces subrutilus species a secondary pathway branching from the manojirimycin precursor results in 1 deoxymanojirimycin via dehydration and reduction of the isomer However Bacillus subtilis does not produce 1 deoxymanojirimycin despite the presence of the manojirimycin precursor 4 Azasugar biosynthesis in Commelina communis involves C1 C5 cyclisation of the original D glucose precursor without the subsequent inversion 4 9 See also editNojirimycin 1 Deoxygalactonojirimycin a stereoisomer of 1 deoxynojirimycinReferences edit KEGG Deoxynojirimycin Chaluntorn Vichasilp et al 2012 Development of high 1 deoxynojirimycin DNJ content mulberry tea and use of response surface methodology to optimize tea making conditions for highest DNJ extraction LWT Food Science and Technology 45 2 226 232 doi 10 1016 j lwt 2011 09 008 Onose S Ikeda R Nakagawa K Kimura T Yamagishi K Higuchi O Miyazawa T 2013 Production of the a glycosidase inhibitor 1 deoxynojirimycin from Bacillus species Food Chemistry 138 1 516 23 doi 10 1016 j foodchem 2012 11 012 PMID 23265519 a b c Gomollon Bel Fernando Delso Ignacio Tejero Tomas Merino Pedro 2014 11 12 Biosynthetic Pathways to Glycosidase Inhibitors Current Chemical Biology 8 1 10 16 doi 10 2174 221279680801141112094818 hdl 10261 122571 ISSN 2212 7968 Kang Kyung Don Cho Yong Seok Song Ji Hye Park Young Shik Lee Jae Yeon Hwang Kyo Yeol Rhee Sang Ki Chung Ji Hyung Kwon Ohsuk June 2011 Identification of the genes involved in 1 deoxynojirimycin synthesis in Bacillus subtilis MORI 3K 85 The Journal of Microbiology 49 3 431 440 doi 10 1007 s12275 011 1238 3 ISSN 1225 8873 PMID 21717329 S2CID 24841974 Kang Kyung Don Cho Yong Seok Song Ji Hye Park Young Shik Lee Jae Yeon Hwang Kyo Yeol Rhee Sang Ki Chung Ji Hyung Kwon Ohsuk June 2011 Identification of the genes involved in 1 deoxynojirimycin synthesis in Bacillus subtilis MORI 3K 85 The Journal of Microbiology 49 3 431 440 doi 10 1007 s12275 011 1238 3 ISSN 1225 8873 PMID 21717329 S2CID 24841974 a b c Clark Lorraine F Johnson Jodie V Horenstein Nicole A 2011 07 22 Identification of a Gene Cluster that Initiates Azasugar Biosynthesis in Bacillus amyloliquefaciens ChemBioChem 12 14 2147 2150 doi 10 1002 cbic 201100347 ISSN 1439 4227 PMID 21786380 S2CID 32186936 a b c Jiang Peixia Mu Shanshan Li Heng Li Youhai Feng Congmin Jin Jian Ming Tang Shuang Yan 2015 02 24 Design and Application of a Novel High throughput Screening Technique for 1 Deoxynojirimycin Scientific Reports 5 1 8563 Bibcode 2015NatSR 5E8563J doi 10 1038 srep08563 ISSN 2045 2322 PMC 4338435 PMID 25708517 a b c Onose Shinji Ikeda Ryoichi Nakagawa Kiyotaka Kimura Toshiyuki Yamagishi Kenji Higuchi Ohki Miyazawa Teruo May 2013 Production of the a glycosidase inhibitor 1 deoxynojirimycin from Bacillus species Food Chemistry 138 1 516 523 doi 10 1016 j foodchem 2012 11 012 ISSN 0308 8146 PMID 23265519 Retrieved from https en wikipedia org w index php title 1 Deoxynojirimycin amp oldid 1198511272, wikipedia, wiki, book, books, library,
