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β-N-乙酰氨基己糖苷酶及其合成寡糖的研究进展
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国家重点基础研究发展计划（国家"973计划"）（2012CB822102）；国家自然科学基金（31670062）


β-N-Acetylhexosaminidases and their application in the synthesis of β-N-acetyl-D-hexosaminides
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    摘要:

    β-N-乙酰氨基己糖苷酶（EC.3.2.1.52）是一类重要的糖苷水解酶，在自然界中催化简单的β-N-乙酰氨基己糖苷或复杂的寡糖链、多糖链中末端N-乙酰己糖苷键的水解，在微生物、植物和动物中广泛分布，具有重要的生物学功能。某些种类的β-N-乙酰氨基己糖苷酶在一定的人为条件下水解β-N-乙酰氨基己糖苷键的同时还具有转糖基作用，能将β-N-乙酰氨基己糖基转移到不同的羟基化合物上，合成β-N-乙酰氨基己糖苷化合物，在糖链合成上具有应用的潜力。本文综述了β-N-乙酰氨基己糖苷酶的结构和催化机制、酶的生物学功能以及酶在β-N-乙酰氨基己糖苷化合物合成中的应用，以促进β-N-乙酰氨基己糖苷酶的进一步研究和开发应用。

    Abstract:

    β-N-Acetylhexosaminidases (EC.3.2.1.52) are an important class of glycosidases that catalyze hydrolysis of terminal N-acetyl-β-D-hexosamine from various oligosaccharides and polysaccharides. These enzymes are widely distributed in microorganisms, plants, and animals, and play crucial roles in nature. Some β-N-acetylhexosaminidases can catalyze glycosyl transfer to form β-N-acetyl-D-hexosaminides, which have shown great potentiality in enzymatic synthesis of functional glycans. In this review, catalytic mechanisms and biological functions of β-N-acetylhexosaminidases, and potential applications of these enzymes in the synthesis of β-N-acetyl-D-hexosaminide are summarized.

    参考文献
    [1] Mega T, Ikenaka T, Matsushima Y. Studies on N-Acetyl-β-D-glucosaminidase of Aspergillus oryzae:I. Purification and characterization of N-Acetyl-β-D-glucosaminidase obtained from takadiastase. The Journal of Biochemistry, 1970, 68(1):109-117.
    [2] Slámová K, Bojarová P, Petrásková L, Křen V. β-N-Acetylhexosaminidase:what's in a name…? Biotechnology Advances, 2010, 28(6):682-693.
    [3] Ferrara MC, Cobucci-Ponzano B, Carpentieri A, Henrissat B, Rossi M, Amoresano A, Moracci M. The identification and molecular characterization of the first archaeal bifunctional exo-β-glucosidase/N-acetyl-β-glucosaminidase demonstrate that family GH116 is made of three functionally distinct subfamilies. Biochimica et Biophysica Acta (BBA)-General Subjects, 2014, 1840(1):367-377.
    [4] Litzinger S, Fischer S, Polzer P, Diederichs K, Welte W, Mayer C. Structural and kinetic analysis of Bacillus subtilis N-acetylglucosaminidase reveals a unique Asp-His dyad mechanism. The Journal of Biological Chemistry, 2010, 285(46):35675-35684.
    [5] Stubbs KA, Balcewich M, Mark BL, Vocadlo DJ. Small molecule inhibitors of a glycoside hydrolase attenuate inducible AmpC-mediated β-lactam resistance. The Journal of Biological Chemistry, 2007, 282(29):21382-21391.
    [6] Bacik JP, Whitworth GE, Stubbs KA, Vocadlo DJ, Mark BL. Active site plasticity within the glycoside hydrolase NagZ underlies a dynamic mechanism of substrate distortion. Chemistry & Biology, 2012, 19(11):1471-1482.
    [7] Mine S, Kado Y, Watanabe M, Fukuda Y, Abe Y, Ueda T, Kawarabayasi Y, Inoue T, Ishikawa K. The structure of hyperthermophilic β-N-acetylglucosaminidase reveals a novel dimer architecture associated with the active site. FEBS Journal, 2014, 281(22):5092-5103.
    [8] Kim JS, Yoon BY, Ahn J, Cha J, Ha NC. Crystal structure of β-N-acetylglucosaminidase CbsA from Thermotoga neapolitana. Biochemical and Biophysical Research Communications, 2015, 464(3):869-874.
    [9] Qin Z, Xiao YB, Yang XB, Mesters JR, Yang SQ, Jiang ZQ. A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3β-N-acetylglucosaminidase. Scientific Reports, 2015, 5:18292.
    [10] Sumida T, Ishii R, Yanagisawa T, Yokoyama S, Ito M. Molecular cloning and crystal structural analysis of a novel β-N-acetylhexosaminidase from Paenibacillus sp. TS12 capable of degrading glycosphingolipids. Journal of Molecular Biology, 2009, 392(1):87-99.
    [11] Tews I, Perrakis A, Oppenheim A, Dauter Z, Wilson KS, Vorgias CE. Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay-Sachs disease. Nature Structural Biology, 1996, 3(7):638-648.
    [12] Langley DB, Harty DWS, Jacques NA, Hunter N, Guss JM, Collyer CA. Structure of N-acetyl-β-D-glucosaminidase (GcnA) from the endocarditis pathogen Streptococcus gordonii and its complex with the mechanism-based inhibitor NAG-thiazoline. Journal of Molecular Biology, 2008, 377(1):104-116.
    [13] Jiang YL, Yu WL, Zhang JW, Frolet C, Di Guilmi AM, Zhou CZ, Vernet T, Chen YX. Structural basis for the substrate specificity of a novel β-N-acetylhexosaminidase StrH protein from Streptococcus pneumoniae R6. The Journal of Biological Chemistry, 2011, 286(50):43004-43012.
    [14] Robb M, Robb CS, Higgins MA, Hobbs JK, Paton JC, Boraston AB. A second β-hexosaminidase encoded in the Streptococcus pneumoniae genome provides an expanded biochemical ability to degrade host glycans. The Journal of Biological Chemistry, 2015, 290(52):30888-30900.
    [15] Pluvinage B, Stubbs KA, Hattie M, Vocadlo DJ, Boraston AB. Inhibition of the family 20 glycoside hydrolase catalytic modules in the Streptococcus pneumoniae exo-β-D-N-acetylglucosaminidase, StrH. Organic & Biomolecular Chemistry, 2013, 11(45):7907-7915.
    [16] Thi NN, Offen WA, Shareck F, Davies GJ, Doucet N. Structure and activity of the Streptomyces coelicolor A3(2) β-N-acetylhexosaminidase provides further insight into GH20 family catalysis and inhibition. Biochemistry, 2014, 53(11):1789-1800.
    [17] Mark BL, Vocadlo DJ, Knapp S, Triggs-Raine BL, Withers SG, James MNG. Crystallographic evidence for substrate-assisted catalysis in a bacterial β-hexosaminidase. The Journal of Biological Chemistry, 2001, 276(13):10330-10337.
    [18] Williams SJ, Mark BL, Vocadlo DJ, James MNG, Withers SG. Aspartate 313 in the Streptomyces plicatus hexosaminidase plays a critical role in substrate-assisted catalysis by orienting the 2-acetamido group and stabilizing the transition state. The Journal of Biological Chemistry, 2002, 277(42):40055-40065.
    [19] Lemieux MJ, Mark BL, Cherney MM, Withers SG, Mahuran DJ, James MNG. Crystallographic structure of human β-hexosaminidase A:interpretation of Tay-Sachs mutations and loss of GM2 ganglioside hydrolysis. Journal of Molecular Biology, 2006, 359(4):913-929.
    [20] Mark BL, Mahuran DJ, Cherney MM, Zhao DL, Knapp S, James MNG. Crystal structure of human β-hexosaminidase B:understanding the molecular basis of Sandhoff and Tay-Sachs disease. Journal of Molecular Biology, 2003, 327(5):1093-1109.
    [21] Liu T, Zhang HT, Liu FY, Wu QY, Shen X, Yang Q. Structural determinants of an insect β-N-Acetyl-D-hexosaminidase specialized as a chitinolytic enzyme. The Journal of Biological Chemistry, 2011, 286(6):4049-4058.
    [22] Ficko-Blean E, Gregg KJ, Adams JJ, Hehemann JH, Czjzek M, Smith SP, Boraston AB. Portrait of an enzyme, a complete structural analysis of a multimodular β-N-acetylglucosaminidase from Clostridium perfringens. The Journal of Biological Chemistry, 2009, 284(15):9876-9884.
    [23] Rao FV, Dorfmueller HC, Villa F, Allwood M, Eggleston IM, van Aalten DMF. Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis. The EMBO Journal, 2006, 25(7):1569-1578.
    [24] Cheng QM, Li HS, Merdek K, Park JT. Molecular characterization of the β-N-acetylglucosaminidase of Escherichia coli and its role in cell wall recycling. Journal of Bacteriology, 2000, 182(17):4836-4840.
    [25] Balcewich MD, Stubbs KA, He Y, James TW, Davies GJ, Vocadlo DJ, Mark BL. Insight into a strategy for attenuating AmpC-mediated β-lactam resistance:Structural basis for selective inhibition of the glycoside hydrolase NagZ. Protein Science, 2009, 18(7):1541-1551.
    [26] Kaplan JB, Ragunath C, Ramasubbu N, Fine DH. Detachment of Actinobacillus actinomycetemcomitans biofilm cells by an endogenous β-hexosaminidase activity. Journal of Bacteriology, 2003, 185(16):4693-4698.
    [27] Ramasubbu N, Thomas LM, Ragunath C, Kaplan JB. Structural analysis of Dispersin B, a biofilm-releasing glycoside hydrolase from the periodontopathogen Actinobacillus actinomycetemcomitans. Journal of Molecular Biology, 2005, 349(3):475-486.
    [28] Sheldon WL, Macauley MS, Taylor EJ, Robinson CE, Charnock SJ, Davies GJ, Vocadlo DJ, Black GW. Functional analysis of a group A streptococcal glycoside hydrolase Spy1600 from family 84 reveals it is a β-N-acetylglucosaminidase and not a hyaluronidase. Biochemical Journal, 2006, 399(2):241-247.
    [29] Rast DM, Baumgartner D, Mayer C, Hollenstein GO. Cell wall-associated enzymes in fungi. Phytochemistry, 2003, 64(2):339-366.
    [30] Rast DM, Horsch M, Furter R, Gooday GW. A complex chitinolytic system in exponentially growing mycelium of Mucor rouxii:properties and function. Journal of General Microbiology, 1991, 137(12):2797-2810.
    [31] Jin YL, Jo YY, Kim KY, Shim JH, Kim YW, Park RD. Purification and characterization of β-N-acetylhexosaminidase from rice seeds. Journal of Biochemistry and Molecular Biology, 2002, 35(3):313-319.
    [32] Oikawa A, Itoh E, Ishihara A, Iwamura H. Purification and characterization of β-N-acetylhexosaminidase from maize seedlings. Journal of Plant Physiology, 2003, 160(9):991-999.
    [33] Hogenkamp DG, Arakane Y, Kramer KJ, Muthukrishnan S, Beeman RW. Characterization and expression of the β-N-acetylhexosaminidase gene family of Tribolium castaneum. Insect Biochemistry and Molecular Biology, 2008, 38(4):478-489.
    [34] Meier EM, Schwarzmann G, Fürst W, Sandhoff K. The human GM2 activator protein. A substrate specific cofactor of β-hexosaminidase A. The Journal of Biological Chemistry, 1991, 266(3):1879-1887.
    [35] Hou YM, Tse R, Mahuran DJ. Direct determination of the substrate specificity of the α-active site in heterodimeric β-hexosaminidase A. Biochemistry, 1996, 35(13):3963-3969.
    [36] Mahuran DJ. Biochemical consequences of mutations causing the GM2 gangliosidoses. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1999, 1455(2/3):105-138.
    [37] Hurtado-Guerrero R, Dorfmueller HC, van Aalten DMF. Molecular mechanisms of O-GlcNAcylation. Current Opinion in Structural Biology, 2008, 18(5):551-557.
    [38] Hart GW, Housley MP, Slawson C. Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins. Nature, 2007, 446(7139):1017-1022.
    [39] Zeidan Q, Hart GW. The intersections between O-GlcNAcylation and phosphorylation:implications for multiple signaling pathways. Journal of Cell Science, 2010, 123(1):13-22.
    [40] Yang WH, Kim JE, Nam HW, Ju JW, Kim HS, Kim YS, Cho JW. Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability. Nature Cell Biology, 2006, 8(10):1074-1083.
    [41] Deng YQ, Li B, Liu F, Iqbal K, Grundke-Iqbal I, Brandt R, Gong CX. Regulation between O-GlcNAcylation and phosphorylation of neurofilament-M and their dysregulation in Alzheimer disease. The FASEB Journal, 2008, 22(1):138-145.
    [42] Liu F, Iqbal K, Grundke-Iqbal I, Hart GW, Gong CX. O-GlcNAcylation regulates phosphorylation of tau:a mechanism involved in Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(29):10804-10809.
    [43] Yuzwa SA, Macauley MS, Heinonen JE, Shan XY, Dennis RJ, He Y, Whitworth GE, Stubbs KA, McEachern EJ, Davies GJ, Vocadlo DJ. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nature Chemical Biology, 2008, 4(8):483-490.
    [44] Yuzwa SA, Vocadlo DJ. O-GlcNAc modification and the tauopathies:insights from chemical biology. Current Alzheimer Research, 2009, 6(5):451-454.
    [45] Dube DH, Bertozzi CR. Glycans in cancer and inflammation-potential for therapeutics and diagnostics. Nature Reviews Drug Discovery, 2005, 4(6):477-488.
    [46] Quiñones-Kochs MI, Buonocore L, Rose JK. Role of N-linked glycans in a human immunodeficiency virus envelope glycoprotein:effects on protein function and the neutralizing antibody response. Journal of Virology, 2002, 76(9):4199-4211.
    [47] Bode L. Human milk oligosaccharides:every baby needs a sugar mama. Glycobiology, 2012, 22(9):1147-1162.
    [48] Fuster MM, Esko JD. The sweet and sour of cancer:glycans as novel therapeutic targets. Nature Reviews Cancer, 2005, 5(7):526-542.
    [49] Wang Y, Zheng X, Tang BZ. Extraction and separation of polysac charides. China Journal of Pharmaceutical Economics, 2013, 8(6):36-38. (in Chinese)王玉, 郑欣, 唐宝珠. 多糖类药物提取及分离分析. 中国药物经济学, 2013, 8(6):36-38.
    [50] Geng YQ, Ye XS. Oligosaccharide synthesis by pre-activation strategy. Progress in Chemistry, 2007, 19(12):1896-1902. (in Chinese)耿轶群, 叶新山. 寡糖合成中的"预活化"策略. 化学进展, 2007, 19(12):1896-1902.
    [51] Sears P, Wong CH. Toward automated synthesis of oligosaccharides and glycoproteins. Science, 2001, 291(5512):2344-2350.
    [52] Trincone A, Giordano A. Glycosyl hydrolases and glycosyltransferases in the synthesis of oligosaccharides. Current Organic Chemistry, 2006, 10(10):1163-1193.
    [53] Singh S, Crout DHG, Packwood J. Enzymatic synthesis of 2-acetamido-4-O-(2-acetamido-2-deoxy-β-D-galactopyranosy l)-2-deoxy-D-glucopyranose and 2-acetamido-6-O-(2-acetamido-2-deoxy-β-D-galactopyranosyl)-2-deoxy-D-glucop yranose catalysed by the β-N-acetylhexosaminidase from Aspergillus oryzae. Carbohydrate Research, 1995, 279:321-325.
    [54] Singh S, Packwood J, Samuel CJ, Critchley P, Crout DHG. Glycosidase-catalysed oligosaccharide synthesis:preparation of N-acetylchitooligosaccharides using the β-N-acetylhexosaminidase of Aspergillus oryzae. Carbohydrate Research, 1995, 279:293-305.
    [55] Uzawa H, Zeng XX, Minoura N. Synthesis of 6'-sulfodisaccharides by β-N-acetylhexosaminidase-catalyzed transglycosylation. Chemical Communications, 2003, 3(1):100-101.
    [56] Aboitiz N, Cañada FJ, Hušáková L, Kuzma M, Křen V, Jiménez-Barbero J. Enzymatic synthesis of complex glycosaminotrioses and study of their molecular recognition by hevein domains. Organic & Biomolecular Chemistry, 2004, 2(14):1987-1994.
    [57] Rauvolfová J, Kuzma M, Weignerová L, Fialová P, Přikrylová V, Pišvejcová A, Macková M, Křen V. β-N-Acetylhexosaminidase-catalysed synthesis of non-reducing oligosaccharides. Journal of Molecular Catalysis B:Enzymatic, 2004, 29(1/6):233-239.
    [58] Lakshmanan T, Loganathan D. Enzymatic synthesis of N-glycoprotein linkage region disaccharide mimetics using β-N-acetylhexosaminidases from Aspergillus oryzae and Vigna radiata. Tetrahedron:Asymmetry, 2005, 16(1):255-260.
    [59] Bojarová P, Slámová K, Křenek K, Gažák R, Kulik N, Ettrich R, Pelantová H, Kuzma M, Riva S, Adámek D, Bezouška K, Křen V. Charged hexosaminides as new substrates for β-N-acetylhexosaminidase-catalyzed synthesis of immunomodulatory disaccharides. Advanced Synthesis & Catalysis, 2011, 353(13):2409-2420.
    [60] Slámová K, Gažák R, Bojarová P, Kulik N, Ettrich R, Pelantová H, Sedmera P, Křen V. 4-Deoxy-substrates for β-N-acetylhexosaminidases:how to make use of their loose specificity. Glycobiology, 2010, 20(8):1002-1009.
    [61] Hušáková L, Riva S, Casali M, Nicotra S, Kuzma M, Huňková Z, Křren V. Enzymatic glycosylation using 6-O-acylated sugar donors and acceptors:β-N-acetylhexosaminidase-catalysed synthesis of 6-O,N,N'-triacetylchitobiose and 6'-O,N,N'-triacetylchitobiose. Carbohydrate Research, 2001, 331(2):143-148.
    [62] Weignerová L, Vavrušková P, Pišvejcová A, Thiem J, Křen V. Fungal β-N-acetylhexosaminidases with high β-N-acetylgalactosaminidase activity and their use for synthesis of β-GalNAc-containing oligosaccharides. Carbohydrate Research, 2003, 338(9):1003-1008.
    [63] Nieder V, Kutzer M, Kren V, Gallego RG, Kamerling JP, Elling L. Screening and characterization of β-N-acetylhexosaminidases for the synthesis of nucleotide-activated disaccharides. Enzyme and Microbial Technology, 2004, 34(5):407-414.
    [64] Matsuo I, Kim S, Yamamoto Y, Ajisaka K, Maruyama JI, Nakajima H, Kitamoto K. Cloning and overexpression of β-N-acetylglucosaminidase encoding gene nagA from Aspergillus oryzae and enzyme-catalyzed synthesis of human milk oligosaccharide. Bioscience, Biotechnology, and Biochemistry, 2003, 67(3):646-650.
    [65] Rauvolfová J, Weignerová L, Kuzma M, Přikrylová V, Macková M, Pišvejcová A, Křen V. Enzymatic synthesis of N-acetylglucosaminobioses by reverse hydrolysis:Characterisation and application of the library of fungal β-N-acetylhexosaminidases. Journal of Molecular Catalysis B:Enzymatic, 2004, 29(1/6):259-264.
    [66] Kurakake M, Goto T, Ashiki K, Suenaga Y, Komaki T. Synthesis of new glycosides by transglycosylation of N-acetylhexosaminidase from Serratia marcescens YS-1. Journal of Agricultural and Food Chemistry, 2003, 51(6):1701-1705.
    [67] Murata T, Tashiro A, Itoh T, Usui T. Enzymic synthesis of 3'-O-and 6'-O-N-acetylglucosaminyl-N-acetyllactosaminide glycosides catalyzed by β-N-acetyl-D-hexosaminidase from Nocardia orientalis. Biochimica et Biophysica Acta (BBA)-General Subjects, 1997, 1335(3):326-334.
    [68] Matahira Y, Tashiro A, Sato T, Kawagishi H, Usui T. Enzymic synthesis of lacto-N-triose Ⅱ and its positional analogues. Glycoconjugate Journal, 1995, 12(5):664-671.
    [69] Chen XD, Xu L, Jin L, Sun B, Gu GF, Lu LL, Xiao M. Efficient and regioselective synthesis of β-GalNAc/GlcNAc-lactose by a bifunctional transglycosylating β-N-acetylhexosaminidase from Bifidobacterium bifidum. Applied and Environmental Microbiology, 2016, 82(18):5642-5652.
    [70] Thomas R, Brooks T. Attachment of Yersinia pestis to human respiratory cell lines is inhibited by certain oligosaccharides. Journal of Medical Microbiology, 2006, 55(3):309-315.
    [71] Thomas R, Brooks T. Common oligosaccharide moieties inhibit the adherence of typical and atypical respiratory pathogens. Journal of Medical Microbiology, 2004, 53(9):833-840.
    [72] Danishefsky SJ, Allen JR. From the laboratory to the clinic:a retrospective on fully synthetic carbohydrate-based anticancer vaccines. Angewandte Chemie International Edition, 2000, 39(5):836-863.
    [73] Wang Z, Wen LJ, Ma X, Chen ZJ, Yu YH, Zhu J, Wang YP, Liu ZM, Liu HY, Wu DP, Zhou DP, Li YS. High expression of lactotriaosylceramide, a differentiation-associated glycosphingolipid, in the bone marrow of acute myeloid leukemia patients. Glycobiology, 2012, 22(7):930-938.
    [74] Zeuner B, Nyffenegger C, Mikkelsen JD, Meyer AS. Thermostable β-galactosidases for the synthesis of human milk oligosaccharides. New Biotechnology, 2016, 33(3):355-360.
    [75] Nyffenegger C, Nordvang RT, Zeuner B, Łęzyk M, Difilippo E, Logtenberg MJ, Schols HA, Meyer AS, Mikkelsen JD. Backbone structures in human milk oligosaccharides:trans-glycosylation by metagenomic β-N-acetylhexosaminidases. Applied Microbiology and Biotechnology, 2015, 99(19):7997-8009.
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陈晓迪,王凤山,肖敏. β-N-乙酰氨基己糖苷酶及其合成寡糖的研究进展[J]. 微生物学报, 2017, 57(8): 1189-1205

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