- freely available
Marine Drugs 2010, 8(11), 2781-2794; doi:10.3390/md8112781
Published: 5 November 2010
Abstract: Sialyltransferases transfer N-acetylneuraminic acid (Neu5Ac) from the common donor substrate of these enzymes, cytidine 5′-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac), to acceptor substrates. The enzymatic reaction products including sialyl-glycoproteins, sialyl-glycolipids and sialyl-oligosaccharides are important molecules in various biological and physiological processes, such as cell-cell recognition, cancer metastasis, and virus infection. Thus, sialyltransferases are thought to be important enzymes in the field of glycobiology. To date, many sialyltransferases and the genes encoding them have been obtained from various sources including mammalian, bacterial and viral sources. During the course of our research, we have detected over 20 bacteria that produce sialyltransferases. Many of the bacteria we isolated from marine environments are classified in the genus Photobacterium or the closely related genus Vibrio. The paper reviews the sialyltransferases obtained mainly from marine bacteria.
Sialic acids are important components of carbohydrate chains and are usually found on the terminal position of the carbohydrate moiety of glycoconjugates, including glycoproteins and glycolipids [1,2]. Many studies have shown that the sialyloligosaccharides of glycoconjugates play significant roles in many biological processes, such as inflammatory and immunological responses, cell–cell recognition, cancer metastasis and viral infection [3–7]. The transferring of sialic acids to carbohydrate chains is performed by specific sialyltransferases in the cell [2,8]. Therefore, the sialyltransferases are considered to be key enzymes in the biosynthesis of sialylated glycoconjugates. Detailed investigations of the biological functions of sialylated-glycoconjugates require an abundant supply of the target compounds. Chemical and enzymatic glycosylation have been the two major routes for the preparation of sialylated-glycoconjugates. Although chemical glycosylation has the advantage of high flexibility and wide applicability, the reaction processes are complicated as the chemical reactions often require multiple protection and de-protection steps [9–11]. On the other hand, enzymatic glycosylation using glycosyltransferases is a single-step process with high positional and anomer selectivity and high reaction yield. For example, in sialylation, the transfer of Neu5Ac by sialyltransferases from CMP-Neu5Ac to the appropriate substrate can be readily achieved under mild reaction conditions . Generally, bacterial enzymes are more stable and productive in Escherichia coli protein expression systems than the mammalian-derived enzymes, and mammalian enzymes have stricter acceptor specificity. Therefore, we have screened many marine bacteria for novel sialyltransferase activity to enzymatically produce sialylated glycoconjugates and sialyloligosaccharides in large amounts. During the course of our research, we have identified over 20 bacteria that produce sialyltransferases, many of which are classified in the genus Photobacterium or the closely related genus Vibrio . Furthermore, we have also revealed that the bacteria-derived sialyltransferases show broader acceptor substrate specificity than the mammalian enzymes . These advantages highlight the capacity of bacterial enzymes to serve as efficient tools for the in vitro enzymatic modification or/and synthesis of sialylated-glycoconjugates and sialyloligosaccharides .
2. Sialic Acid
2.1. Structure and distribution
Sialic acids (Sias) are a family of monosaccharides comprising over 50 naturally occurring derivatives of neuraminic acid, 5-amino-3,5-dideoxy-d-glycero-d-galacto-2-nonulosonic acid (Neu) [1,2]. Structurally, the Sia derivatives of Neu carry a variety of substitutions at the amino and/or hydroxyl groups. The amino acid group is often acetylated, glycolylated, or replaced by a hydroxyl group. The hydroxyl groups can be acetylated at O4, O7, O8, or O9, singly or in combination , and can also be modified by acetate, lactate, phosphate or sulfate esters.
The three major members of the Sia group are N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc), and 2-keto-3-deoxy-d-glycero-d-galacto-nonulosonic acid (KDN) [1,2]. Although, Sias are widely distributed in higher animals and some microorganisms, only Neu5Ac is ubiquitous, and Neu5Gc is not found in bacteria . Usually, Sias exist in the carbohydrate moiety of glycoconjugates, and are linked to the terminal positions of the carbohydrate chains of the glycoconjugates . The structures of three major sialic acids are described in Figure 1.
2.2. Importance of sialyloligosaccharides
In the sialylated glycoconjugates, mainly four linkage patterns, including Neu5Acα2-6Gal, Neu5Acα2-3Gal, Neu5Acα2-6GalNAc, and Neu5Acα2-8Neu5Ac, are found [1,2]. These structures are formed by specific sialyltransferases in the cell. As described above, sialyloligosaccharides of glycoconjugates play important roles in many biological processes. For example, the relationship between the structure of carbohydrate chains and the recognition of the host cell by influenza virus is one of the best understood biological phenomena. Many studies have shown that influenza A and B viruses bind to cell surface receptors of host cells via Neu5Ac-linked glycoproteins or glycolipids through viral hemagglutinin recognition of host cell Neu5Ac [14–16]. Furthermore, it has been clearly demonstrated that these influenza viruses also recognize the carbohydrate chain structure of the host cell . For example, the avian influenza viruses recognize Neu5Acα2-3Galβ1-3/4GlcNAc structures, and the human influenza viruses recognize Neu5Acα2-6Galβ1-3/4GlcNAc structures [14,15]. The host cell specificity of the influenza viruses is determined mainly by the linkage of Neu5Ac to the penultimate galactose residues and core structures. Thus, the distribution of Neu5Ac and its linkage patterns on the host cell surface are important determinants of host tropism [17,18].
3.1. Classes and sources sialyltransferases
To date, many sialyltransferases have been obtained from mammals, bacteria and viruses [8,19,20]. They are classified into four families according to the carbohydrate linkages they synthesize: the beta-galactoside α2,3-sialyltransferases (ST3Gal I–VI), the beta-galactoside α2,6-sialyltransferases (ST6Gal I, II), the GalNAc α2,6-sialyltransferases (ST6GalNAc I–VI), and the α2,8-sialyltransferases (ST8Sia I–VI) . On the other hand, all the sialyltransferases have been also classified into five families on the basis of sequence similarities in the CAZy (carbohydrate-active enzymes) database , i.e., glycosyltransferase family (GT) 29, various sialyltransferases from eukaryotes and viruses; family 38, polysialyltransferase from bacteria such as Escherichia coli; family 42, lipooligosaccharide α2,3-sialyltransferase from bacteria such as Campylobacter jejuni; family 52, α2,3-sialyltransferase from bacteria such as Neisseria gonorrhoeae; and family 80, α2,6-sialyltransferase from marine bacteria such as Photobacterium damselae.
It has been revealed that mammalian sialyltransferases contain conserved sequence motifs, including sialyl motifs L, S, VS and motif III [22–24]. Very recently, a crystal structure of the mammalian sialyltransferase was reported . Some functions of these motifs have been clarified. For example, mutagenesis studies have demonstrated that motif L is involved in donor substrate binding  and that motif S is involved in donor and acceptor substrate binding . Like the mammalian sialyltransferases, viral α2,3-sialyltransferase, obtained from myxoma-virus-infected RK13 cells, contains the motifs L and S in its catalytic domain and is closely related to mammalian α2,3-sialyltransferase (ST3Gal IV) on the basis of amino acid sequence similarity . The substrate specificity of the viral and mammalian sialyltransferases is very different, despite the common presence of the sialyl motifs.
The known bacterial sialyltransferases do not contain the sialyl motifs found in mammalian sialyltransferases [19,20]. Two short motifs, referred to as the D/E-D/E-G and HP motifs, have been recently identified in the bacterial sialyltransferases and are shown to be functionally important for enzyme catalysis and donor substrate binding . These two motifs are structurally distinct from the motifs found in mammalian sialyltransferases. Furthermore, it has been also demonstrated that the three conserved functional motifs, named YDDGS motif, FKGHP motif and SS motif, exist in the bacterial sialyltransferases that have been classified into GT family 80 .
3.2. Classification of sialyltransferases produced by bacteria
Genes encoding sialyltransferases have been cloned from various types of bacteria, including N. gonorrhoeae , Neisseria meningitidis , C. jejuni , E. coli , P. damselae , Photobacterium phosphoreum , Photobacterium leiognathi [35,36], Photobacterium sp. , Vibrio sp. , Pasteurella multocida , Haemophilus influenzae , and Streptococcus agalactiae . As described above, all bacterial sialyltransferases are classified into four families in the CAZy database: (1) glycosyltransferase (GT) family 38 (polysialyltransferase from E. coli and N. meningitidis); (2) GT family 42 (lipooligosaccharide α2,3-sialyltransferase and α2,3-/α2,8-sialyltransferase from C. jejuni and H. influenzae); (3) GT family 52 (α2,3-sialyltransferase from H. influenzae, N. gonorrhoeae, and N. meningitidis); and (4) GT family 80 (α2,6-sialyltransferase and α2,3-/α2,6-sialyltransferase from P. damselae and P. multocida). Some marine bacterial sialyltransferases also show both sialyltransferase and neuraminidase activities. The relationship between the marine bacterial sialyltransferases and type of enzyme activities is listed in Table 1.
Recently, it has been also reported that marine bacteria producing α2,6-sialyltransferases express Neu5Ac residue on their cell surfaces . Among the bacteria producing α2,6-sialyltransferases, P. damselae is known as a causative agent of wound infection, ulceration and pasteurellosis [43–45]. As described in the introduction, sialyloligosaccharides are important molecules for cell–cell interaction and infection. Although the structures of the sialyloligosaccharides produced by the bacteria are still unknown, the molecules containing Neu5Ac on their cell surfaces that might be produced by the enzymes may be involved in virulence and adhesion to host cells.
4. Enzymatic Properties of Marine Bacterial Sialyltransferases
4.1. An α2,6-sialyltransferase produced by P. damselae JT0160
To date, it has been demonstrated that the α2,6-sialyltransferase produced by P. damselae JT0160 has unique acceptor substrate specificity compared with the mammalian counterparts. First, it has been revealed that P. damselae α2,6-sialyltransferase transfers Neu5Ac to both glycoproteins including asialo-N-linked and asialo-O-linked glycoproteins and glycolipids [46,47]. However, rat liver α2,6-sialyltransferase has a Km value approximately 33-times higher for lactose than for N-acetyllactosaminide, P. damselae α2,6-sialyltransferase recognizes lactose and N-acetyllactosaminide as acceptor substrates with almost equal Km values . These result indicates that P. damselae α2,6-sialyltransferase does not recognize the 2-acetamido group in the N-acetylglucosaminyl residue, unlike the mammalian enzymes. The acceptor substrate specificity of mammalian sialyltransferases is generally high, and mammalian enzymes are specific for the type of the sugars and linkages. For example, mammalian sialyltransferases do not recognize fucosylated carbohydrate chains as an acceptor substrate. In eukaryotes, the carbohydrate chain moieties of glycoconjugate are synthesized by a series of glycosyltransferases, and the order of glycosylation is determined strictly. Usually, fucosylation is performed by fucosyltransferases after sialylation in mammalian cell. Thus, mammalian sialyltransferases do not recognize fucosylated carbohydrate chain as acceptor substrates and cannot transfer Neu5Ac to them. However, P. damselae α2,6-sialyltransferase does recognizes fucosylated carbohydrate chains as an acceptor substrate and transfers Neu5Ac to the galactose residue of carbohydrate chains at position 6 in 2′-fucosyllactose . In addition, the α2,6-sialyltransferase also recognizes 3′-sialyllactose and gives 3′,6′-disialyllactose as the reaction product . The structures of the reaction products derived from 2′-fucosyllactose and 3′-sialyllactose are described in Figure 2.
The P. damselae α2,6-sialyltransferase is less specific, which may allow various sialylated glycans to be prepared, as described above. Furthermore, it has been revealed that the α2,6-sialyltransferase uses both Galβ1,3GlcNAc and Galβ1,6GlcNAc as acceptor substrates and gives the corresponding enzymatic reaction products, respectively . These results indicate that this α2,6-sialyltransferase is not sensitive to the nature of the second sugar from the non-reducing terminus and to the linkage between the terminal two sugars. The structures of the reaction products derived from Galβ1,3GlcNAc and Galβ1,6GlcNAc are described in Figure 3.
It has been also revealed that the α2,6-sialyltransferase has unique donor substrate specificity. The sialyltransferase recognizes CMP-Neu5Ac, CMP-KDN as donor substrates and many CMP-sialic acid derivatives with the non-natural modification of an azido or acetylene group at positions C5, C7, C8, and/or C9 [51,52].
4.2. An α2,6-sialyltransferase produced by Photobacterium sp. JT-ISH-224
Except α2,6-sialyltransferase produced by P. damselae JT0160, three additional genes encoding the marine bacterial α2,6-sialyltransferase have been cloned from Photobacterium sp. JT-ISH-224 , P. leiognathi JT-SHIZ-145  and P. leiognathi JT-SHIZ-119 . These genes have all been expressed as recombinant active form enzymes in an E. coli protein expression system. Among them, α2,6-sialyltransferase cloned from Photobacterium sp. JT-ISH-224 has been shown to display the highest specific activity. A homology search shows that the amino acid sequence of the α2,6-sialyltransferase from JT-ISH-224 has 54% identity to α2,6-sialyltransferase cloned from P. damselae JT0160. The enzymatic property of the α2,6-sialyltransferase cloned from Photobacterium sp. JT-ISH-224 is similar to that of the α2,6-sialyltransferase cloned from P. damselae JT0160. To date, it has been revealed that the α2,6-sialyltransferase cloned from JT-ISH-224 can transfer Neu5Ac to both O-6 and O-6′ hydroxyl groups of lactose simultaneously and gives 6,6′-disialyllactose, and transfers KDO (2-keto-3-deoxyoctonate) to the O-6′ hydroxyl group of lactose and gives KDO-lactose . The structures of the reaction products described here are shown in Figure 4.
4.3. An α2,3-sialyltransferase produced by P. phosphoreum JT-ISH-467
To date, three genes encoding the marine bacterial α2,3-sialyltransferase have been cloned from Photobacterium sp. JT-ISH-224 , P. phosphoreum JT-ISH-467  and Vibrio sp. JT-FAJ-16  and all these genes have been expressed as recombinant active form enzymes in an E. coli protein expression system. During the course of 3′-sialyllactose production using α2,3-sialyltransferase cloned from Photobacterium sp. JT-ISH-224, it has been revealed that the α2,3-sialyltransferase can transfer Neu5Ac to both O-2 and O-3′ hydroxyl groups of lactose simultaneously, giving 2,3′-disialyllactose as an enzymatic reaction product . By NMR spectroscopy analysis, it has been confirmed that the reaction product contain only α-form. The relative configuration between C-1 to C-3 of the α-glucopyranose residue is superimposable with that between C-4 to C-2 of galactopyranose. Therefore, it is expected that the enzyme recognizes the α-glucopyranose residue as acceptor substrate and transfers Neu5Ac to O-2 hydroxyl group of the α-glucopyranose. In addition, it has been also demonstrated that the α2,3-sialyltransferase can transfer Neu5Ac to the β-anomeric hydroxyl groups of mannose and gives the corresponding reaction product . In this case, the stereochemistry of β-mannose residue from C-2 to O-5 in the pyranose ring is superimposable on that from C-4 to C-2 of galactopyranose, except for the difference between the C-2 carbon atom in the Gal and O-5 oxygen atom in the Man . Thus, it is strongly expected that the α2,3-sialyltransferase recognizes the acceptor substrate mainly through the stereochemical structure of the C-4 to C-3 of Gal . The structures of the reaction products produced by the enzyme are shown in Figure 5.
Very recently, it has been also reported that this α2,3-sialyltransferase can catalyze the transfer of Neu5Ac residue to inositols, non-carbohydrates, as well as to carbohydrates with a diol structure corresponding to the C-3 and C-4 of the galactopyranose moiety. As described, the α2,3-sialyltransferase does recognizes both epi-inositol and 1D-chiro-inositol as acceptor substrates, and gives the corresponding reaction products . The structures of the reaction products derived from epi-inositol and 1D-chiro-inositol are described in Figure 6.
5. Application of Sialyltransferases
5.1. Production of sialyloligosaccharides
A remarkable oligosaccharide production method has been reported using a single growing metabolically engineered bacterium . In this method, oligosaccharides are produced in a bacterium that overexpresses the recombinant glycosyltransferase genes and that maintains the pool level of the sugar nucleotides by its enzymatic cellular machinery [57,58]. To date, it has been reported that several oligosaccharides, such as lacto-N-neotetraose, lacto-N-neoheaxose, and sialyllactose, are efficiently produced by this method using bacterial glycosyltransferases, such as β1,3-N-acetylglucosaminyltransferase, β1,4-galactosyltransferase and α2,3-sialyltransferase from N. meningitidis, α1,2-fucosyltransferase from Helicobacter pylori, etc.[56–58]. Very recently, it has been also reported that more than 25 g/L of both 6′-sialyllactose and 3′-sialyllactose have been produced by a high-density cell culture of E. coli strains overexpressing bacterial sialyltransferases of α2,6-sialyltransferase from Photobacterium sp. and α2,3-sialyltransferase from N. meningitidis, respectively [53,59]. In the case of the sialyllactose production system using the transformed bacterium by Photobacterium sp. JT-ISH-224 α2,6-sialyltransferase gene, formation of KDO-lactose and 6,6′-disialyllactose has been observed as well as 6′-sialyllactose production . On the other hand, no formation of by-product has been observed in case of sialyllactose production system using the transformed bacterium by the N. meningitidis α2,3-sialyltransferase gene. These results indicate that the 6′-sialyllactose production system with marine bacterial sialyltransferase has the possibility to produce various kinds of sialylated carbohydrate chains, but examination of the culture conditions are necessary to efficiently produce the compounds aimed for .
5.2. Application of sialyloligosaccharides
As described above, influenza A and B viruses infect host cells through the binding of viral hemagglutinins to sialylglycoproteins or sialylglycolipids of the receptors on the host cell surface [7,14–18]. These influenza viruses recognize both sialic acid in the receptor on the cell surface and carbohydrate chain structures on the cell surface including Neu5Acα2-3(6)Galβ1-3GlcNAc (sialyl-lacto series Type I) or Neu5Acα2-3(6)Galβ1-4GlcNAc (sialyl-lacto series Type II). Therefore, molecules with the carbohydrate chain structures described above are thought to be potential inhibitors of infection by influenza virus or to be materials for influenza virus adsorption . In addition, the ability of influenza viruses to recognize sialyloligosaccharides is known to be enhanced by the clustering of sialyloligosaccharides on macromolecules . Thus, a variety of glycopolymers with multivalent sialyloligosaccharides that target influenza viral hemagglutinines have been synthesized for developing influenza virus inhibitors or adsorption materials . Up to present, various glycopolymers carrying sialyloligosaccharides have been produced using polyacrylamide, γ-polyglutamic acid, polystyrene, chitosan and dendrimers as the polymer backbone, and their inhibition of influenza virus infection has also been demonstrated [60–68].
Recently, it has been clearly demonstrated that sialyllactose (Neu5Acα2-3(6)Galβ1-4Glc), Neu5Ac and N-acetylmannosamine could be candidates for prophylactic drugs to distal myopathy with rimmed vacuoles (DMRV)-hereditary inclusion body myopathy (hIBM), which is a moderately progressive autosomal recessive myopathy . The disease gene underlying DMRV-hIBM has been predicted to be GNE, encoding UDP-N-acetylglucosamine-2-epimerase and N-acetylmannosamine kinase [70,71]. These enzymes are essential for sialic acid biosynthesis. Thus, the patients who have this disease show hyposialylation in various organs . A prophylactic treatment with sialyllactose, Neu5Ac and N-acetylmannosamine was tested to confirm effectiveness in a mouse model of DMRV-hIBM. Oral treatment with the sialic acid metabolites described above completely precluded the development of the myopathic phenotype in the model mice . Therefore, it is strongly expected that DMRV-hIBM in humans can potentially be treated by oral addition of sialic acid metabolites, such as sialyllactose, Neu5Ac and N-acetylmannosamine, and their derivatives.
The author would like to thank all of his colleagues and collaborators.
- Schauer, R. Sialic acid: fascinating sugars in higher animals and man. Zoology 2004, 107, 49–64, doi:10.1016/j.zool.2003.10.002. 16351927
- Angata, T; Varki, A. Chemical diversity in the sialic acids and related α-keto acids: an evolutionary perspective. Chem Rev 2002, 102, 439–469, doi:10.1021/cr000407m. 11841250
- Paulson, JC. Glycoproteins: What are the sugar chains for. Trends Biochem Sci 1989, 14, 272–276, doi:10.1016/0968-0004(89)90062-5. 2672447
- Hakomori, S. Bifunctional role of glycosphingolipids. J Biol Chem 1990, 265, 18713–18716. 2229037
- Lasky, LA. Selectins: Interpreters of cell-specific carbohydrate information during inflammation. Science 1992, 258, 964–969, doi:10.1126/science.1439808. 1439808
- Kannagi, R. Regulatory roles of carbohydrate ligands for selectins in homing of lymphocytes. Curr Opin Struct Biol 2002, 12, 599–608, doi:10.1016/S0959-440X(02)00365-2. 12464311
- Suzuki, Y. Sialobiology of influenza: molecular mechanism of host range variation of influenza virus. Biol Pharm Bull 2005, 28, 399–408, doi:10.1248/bpb.28.399. 15744059
- Taniguchi, N; Honke, K; Fukuda, M. Handbook of Glycosyltransferases and Related Genes, 1st ed ed.; Springer-Verlag: Tokyo, Japan, 2002; pp. 267–356.
- Schmidt, RR. New methods for the synthesis of glycosides and oligosaccharides—Are there alternatives to the Koenigs-Knorr method? New Synthetic Methods. Angew Chem Int Ed Engl 1986, 25, 212–235, doi:10.1002/anie.198602121.
- Kanie, O; Hindsgaul, O. Synthesis of oligosaccharides, glycolipids and glycopeptides. Curr Opin Struct Biol 1992, 2, 674–681, doi:10.1016/0959-440X(92)90200-Q.
- Wang, Z; Zhang, X-F; Ito, Y; Nakahara, Y; Ogawa, T. A new strategy for stereoselective synthesis of sialic acid-containing glycopeptide fragment. Bioorg Med Chem 1996, 4, 1901–1908, doi:10.1016/S0968-0896(96)00172-1. 9007274
- Izumi, M; Wong, C-H. Microbial sialyltransferases for carbohydrate synthesis. Trends Glycosci Glycotechnol 2001, 13, 345–360, doi:10.4052/tigg.13.345.
- Yamamoto, T; Takakura, Y; Tsukamoto, H. Bacterial sialyltransferase. Trends Glycosci Glycotechnol 2006, 18, 253–265, doi:10.4052/tigg.18.253.
- Connor, RJ; Kawaoka, Y; Webster, RG; Paulson, JC. Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 1994, 205, 17–23, doi:10.1006/viro.1994.1615. 7975212
- Rogers, GN; Paulson, JC. Receptor determinations of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 1983, 127, 361–373, doi:10.1016/0042-6822(83)90150-2. 6868370
- Suzuki, Y; Ito, T; Suzuki, T; Holland, RE, Jr; Chambers, TM; Kiso, M; Ishida, H; Kawaoka, Y. Sialic acid species as a determinant of the host range of influenza A virus. J Virol 2000, 74, 11825–11831, doi:10.1128/JVI.74.24.11825-11831.2000. 11090182
- Yamada, S; Suzuki, Y; Suzuki, T; Li, MQ; Nidom, CA; Sakai-Tagawa, Y; Muramoto, Y; Ito, M; Kiso, M; Hiromoto, T; et al. Hemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature 2006, 444, 378–382, doi:10.1038/nature05264. 17108965
- Suzuki, Y. Gangliosides as influenza virus receptors. Variation of influenza viruses and their recognition of the receptor sialo-sugar chains. Prog Lipid Res 1994, 33, 429–457, doi:10.1016/0163-7827(94)90026-4. 7870741
- Koizumi, S. Large-scale production of oligosaccharides using bacterial functions. Trends Glycosci Glycotechnol 2003, 15, 65–74, doi:10.4052/tigg.15.65.
- Sujino, K; Jackson, RJ; Chan, NWC; Tsuji, S; Palcic, MM. A novel viral α2,3-sialyltransferase (v-ST3Gal I): Transfer of sialic acid to fucosylated acceptors. Glycobiology 2000, 10, 313–320, doi:10.1093/glycob/10.3.313. 10704530
- Coutinho, PM; Deleury, E; Davies, GJ; Henrissat, B. An evolving hierarchical family classification for glycosyltransferases. J Mol Biol 2003, 328, 307–317, doi:10.1016/S0022-2836(03)00307-3. 12691742
- Datta, AK; Sinha, A; Paulson, JC. Mutation of the sialyltransferase S-sialylmotif alters the kinetics of the donor and acceptor substrates. J Biol Chem 1998, 273, 9608–9618, doi:10.1074/jbc.273.16.9608. 9545292
- Sasaki, K. Molecular cloning and characterization of sialyltransferase. Trends Glycosci Glycotechnol 1996, 8, 195–215, doi:10.4052/tigg.8.195.
- Jeanneau, C; Chazalet, V; Augé, C; Soumpasis, DM; Harduin-Lepers, A; Delannoy, P; Imberty, A; Breton, C. Structure-function analysis of the human sialyltransferase ST3Gal I: role of N-glycosylation and a novel conserved sialylmotif. J Biol Chem 2004, 279, 13461–13468, doi:10.1074/jbc.M311764200. 14722111
- Rao, FV; Rich, JR; Rakić, B; Buddai, S; Schwartz, MF; Johnson, K; Bowe, C; Wakarchuk, WW; Defrees, S; Withers, SG; Strynadka, NC. Structural insight into mammalian sialyltransferases. Nat Struct Mol Biol 2009, 16, 1186–1188, doi:10.1038/nsmb.1685. 19820709
- Datta, AK; Paulson, JC. The sialyltransferase “Sialylmotif” participates in binding the donor substrate CMP-NeuAc. J Biol Chem 1995, 270, 1497–1500, doi:10.1074/jbc.270.4.1497. 7829476
- Freiberger, F; Claus, H; Gunzel, A; Oltmann-Norden, I; Vionnet, J; Muhlenhoff, M; Vogel, U; Vann, WF; Gerardy-Schahn, R; Stummeyer, K. Biochemical characterization of a Neisseria meningitidis polysialyltransferase reveals novel functional motifs in bacterial sialyltransferases. Mol Microbiol 2007, 65, 1258–1275, doi:10.1111/j.1365-2958.2007.05862.x. 17662040
- Yamamoto, T; Ichikawa, M; Takakura, Y. Conserved amino acid sequences in the bacterial sialyltransferases belonging to Glycosyltransferase family 80. Biochem Biophys Res Commun 2008, 365, 340–343, doi:10.1016/j.bbrc.2007.10.201. 17997982
- Gilbert, M; Watson, DC; Cunningham, AM; Jennings, MP; Young, NM; Wakarchuk, WW. Cloning of the lipooligosaccharide α-2,3-sialyltransferase from the bacterial pathogens Neisseria meningitidis and Neisseria gonorrhoeae. J Biol Chem 1996, 271, 28271–28276, doi:10.1074/jbc.271.45.28271. 8910446
- Edwards, U; Muller, A; Hammerschmidt, S; Gerardy-Schahn, R; Frosch, M. Molecular analysis of the biosynthesis pathway of the (α-2,8) polysialic acid capsule by Neisseria meningitidis serogroup B. Mol Microbiol 1994, 14, 141–149, doi:10.1111/j.1365-2958.1994.tb01274.x. 7830552
- Gilbert, M; Brisson, JR; Karwaski, MF; Michniewicz, J; Cunningham, AM; Wu, Y; Young, NM; Wakarchuk, WW. Biosynthesis of ganglioside mimics in Campylobacter jejuni OH 4384: Identification of the glycosyltransferase genes, enzymatic synthesis of model compounds, and characterization of nanomole amounts by 600-MHz 1H and 13C NMR analysis. J Biol Chem 2000, 275, 3896–3906, doi:10.1074/jbc.275.6.3896. 10660542
- Shen, GJ; Datta, AK; Izumi, M; Koeller, KM; Wong, C-H. Expression of α2,8/2,9-Polysialyltransferase from Escherichia coli K92. characterization of the enzyme and its reaction products. J Biol Chem 1999, 274, 35139–35146, doi:10.1074/jbc.274.49.35139. 10574996
- Yamamoto, T; Nakashizuka, M; Terada, I. Cloning and expression of a marine bacterial β-galactoside α2,6-sialyltransferase gene from Photobacterium damsela JT0160. J Biochem 1998, 123, 94–100, doi:10.1093/oxfordjournals.jbchem.a021921. 9504414
- Tsukamoto, H; Takakura, Y; Yamamoto, T. Purification, cloning and expression of an α-/β-galactoside α2,3-sialyltransferase from a luminous marine bacterium Photobacterium phosphoreum. J Biol Chem 2007, 282, 29794–29802, doi:10.1074/jbc.M701907200. 17702755
- Yamamoto, T; Hamada, Y; Ichikawa, M; Kajiwara, H; Mine, T; Tsukamoto, H; Takakura, Y. A β-galactoside α2,6-sialyltransferase produced by a marine bacterium, Photobacterium leiognathi JTSHIZ-145, is active at pH 8. Glycobiology 2007, 17, 1167–1174, doi:10.1093/glycob/cwm086. 17704107
- Mine, T; Katayama, S; Kajiwara, H; Tsunashima, M; Tsukamoto, T; Takakura, Y; Yamamoto, T. An α2,6-sialyltransferase cloned from Photobacterium leiognathi strain JT-SHIZ-119 shows both sialyltransferase and neuraminidase activity. Glycobiology 2010, 20, 158–165, doi:10.1093/glycob/cwp157. 19797322
- Tsukamoto, H; Takakura, Y; Mine, T; Yamamoto, T. Photobacterium sp. JT-ISH-224 Produces Two Sialyltransferases, α-/β-Galactoside α2,3-Sialyltransferase and β-Galactoside α2,6-Sialyltransferase. J Biochem 2008, 143, 187–197. 17984122
- Takakura, Y; Tsukamoto, H; Yamamoto, T. Molecular cloning, expression and properties of an α/β-galactoside α2,3-sialyltransferase from Vibrio sp. JT-FAJ-16. J Biochem 2007, 142, 403–412, doi:10.1093/jb/mvm147. 17673486
- Yu, H; Chokhawala, H; Karpel, R; Yu, H; Wu, B; Zhang, J; Zhang, Y; Jia, Q; Chen, X. A multifunctional Pasteurella multocida sialyltransferase: A powerful tool for the synthesis of sialoside libraries. J Am Chem Soc 2005, 127, 17618–17619, doi:10.1021/ja0561690. 16351087
- Hood, DW; Cox, AD; Gilbert, M; Makepeace, K; Walsh, S; Deadman, ME; Cody, A; Martin, A; Mansson, M; Schweda, EK; Brisson, JR; Richards, JC; Moxon, ER; Wakarchuk, WW. Identification of a lipopolysaccharide α-2,3-sialyltransferase from Haemophilus influenzae. Mol Microbiol 2001, 39, 341–350, doi:10.1046/j.1365-2958.2001.02204.x. 11136455
- Watanabe, M; Miyake, K; Yamamoto, S; Kataoka, Y; Koizumi, S; Endo, T; Ozaki, A; Iijima, S. Identification of sialyltransferases of Streptococcus agalactiae. J Biosci Bioeng 2002, 93, 610–613. 16233258
- Kajiwara, H; Toda, M; Mine, T; Nakada, H; Wariishi, H; Yamamoto, T. Visualization of sialic acid produced on bacterial cell surfaces by lectin staining. Microbes Environ 2010, 25, 152–155, doi:10.1264/jsme2.ME10118. 21576867
- Austin, B. Vibrios as causal agents of zoonoses. Vet Microbiol 2010, 140, 310–317, doi:10.1016/j.vetmic.2009.03.015. 19342185
- Jung, TS; Thompson, KD; Adams, A. A comparison of sialic acid between different isolates of Photobacterium damselae subsp. piscicida. Fish Pathol 2001, 36, 217–224, doi:10.3147/jsfp.36.217.
- Love, M; Teebken-Fisher, D; Mecca, M. The marine bacterium Vibrio damselae sp. causes skin ulcers on the damselfish Chromis punctipinnis: Association with human infections. Science 1981, 214, 1139–1140, doi:10.1126/science.214.4525.1139. 17755898
- Yamamoto, T; Nagae, H; Kajihara, Y; Terada, I. Mass production of bacterial α2,6-sialyltransferase and enzymatic syntheses of sialyloligosaccharides. Biosci Biotechnol Biochem 1998, 62, 210–214, doi:10.1271/bbb.62.210. 9532777
- Kushi, Y; Kamimiya, H; Hiratsuka, H; Nozaki, H; Fukui, H; Yanagida, M; Hashimoto, M; Nakamura, K; Watarai, S; Kasama, T; Kajiwara, H; Yamamoto, T. Sialyltransferases of marine bacteria efficiently utilize glycosphingolipid substrates. Glycobiology 2010, 20, 187–198, doi:10.1093/glycob/cwp160. 19837852
- Yamamoto, T; Nakashizuka, M; Kodama, H; Kajihara, Y; Terada, I. Purification and characterization of a marine bacterial β-galactoside α2,6-sialyltransferase from Photobacterium damsela JT0160. J Biochem 1996, 120, 104–110, doi:10.1093/oxfordjournals.jbchem.a021370. 8864851
- Kajihara, Y; Yamamoto, T; Nagae, H; Nakashizuka, M; Sakakibara, T; Terada, I. A Novel α2,6-Sialyltransferase: Transfer of Sialic Acid to Fucosyl and Sialyl Trisaccharides. J Org Chem 1996, 61, 8632–8635, doi:10.1021/jo961214v.
- Mine, T; Miyazaki, T; Kajiwara, H; Naito, K; Ajisaka, K; Yamamoto, T. Enzymatic synthesis of unique sialyloligosaccharides using marine bacterial α-(2→3)- and α-(2→6)-sialyltransferases. Carbohydr Res 2010, 345, 1417–1421, doi:10.1016/j.carres.2010.03.036. 20413108
- Kajihara, Y; Akai, S; Nakagawa, T; Sato, R; Ebata, T; Kodama, H; Sato, K. Enzymatic synthesis of Kdn oligosaccharides by a bacterial α-(2→6)-sialyltransferase. Carbohydr Res 1999, 315, 137–141, doi:10.1016/S0008-6215(98)00331-0. 10385976
- Yu, H; Huang, S; Chokhawala, H; Sun, M; Zheng, H; Chen, X. Highly efficient chemoenzymatic synthesis of naturally occurring and non-natural alpha-2,6-linked sialosides: A P. damsela alpha-2,6-sialyltransferase with extremely flexible donor-substrate specificity. Angew Chem Int Ed Engl 2006, 45, 3938–3944, doi:10.1002/anie.200600572. 16721893
- Drouillard, S; Mine, T; Kajiwara, H; Yamamoto, T; Samain, E. Efficient synthesis of 6′-sialyllactose, 6′,6-disialyllactose and 6′-KDO-lactose by metabolically engineered Escherihiae coli expressing a multifunctional sialyltransferase from the Photobacterium sp. JT-ISH-224. Carbohydr Res 2010, 345, 1394–1399, doi:10.1016/j.carres.2010.02.018. 20231015
- Mine, T; Kajiwara, H; Murase, T; Kajihara, Y; Yamamoto, T. An α2,3-sialyltransferase cloned from Photobacterium sp. JT-ISH-224 transfers N-acetylneuraminic acid to both O-2 and O-3′ hydroxyl groups of lactose. J Carbohydr Chem 2010, 29, 51–60, doi:10.1080/07328300903586422.
- Mine, T; Miyazaki, T; Kajiwara, H; Tateda, N; Ajisaka, K; Yamamoto, T. A recombinant α-(2→3)-sialyltransferase with an extremely broad acceptor substrate specificity from Photobacterium sp. JT-ISH-224 can transfer N-acetylneuraminic acid to inositols. Carbohydr Res 2010, 345, 2485–2490, doi:10.1016/j.carres.2010.09.022. 20947069
- Preim, B; Gilbert, M; Wakarchuk, WW; Heyraud, A; Samain, E. A new fermentation process allows large scale production of human milk oligosaccharides by metabolically engineered bacteria. Glycobiology 2002, 12, 235–240, doi:10.1093/glycob/12.4.235. 12042246
- Antoine, T; Priem, B; Heyraud, A; Greffe, L; Gilbert, M; Wakarchuk, WW; Lam, JS; Samain, E. Large-scale in vivo synthesis of the carbohydrate moieties of gangliosides GM1 and GM2 by metabolically engineered Escherichia coli. Chembiochem 2003, 4, 406–412, doi:10.1002/cbic.200200540. 12740812
- Drouillard, S; Driguez, H; Samain, E. Large-scale synthesis of H-antigen oligosaccharides by expressing Helicobacter pylori alpha1,2-fucosyltransferase in metabolically engineered Escherichia coli cells. Angew Chem Int Ed Engl 2006, 45, 1778–1780, doi:10.1002/anie.200503427. 16477664
- Fierfort, N; Samain, E. Genetic engineering of Escherichia coli for the economical production of sialylated oligosaccharides. J Biotechnol 2008, 134, 261–265, doi:10.1016/j.jbiotec.2008.02.010. 18378033
- Tsuchida, A; Kobayashi, K; Matsubara, N; Muramatsu, T; Suzuki, T; Suzuki, Y. Simple synthesis of sialyllactose-carrying polystyrene and its binding with influenza virus. Glycoconj J 1998, 15, 1047–1054, doi:10.1023/A:1006960116583. 10386889
- Sigal, GB; Mammen, M; Dahmann, G; Whitesides, GM. Polyacrylamides bearing pendant α-sialoside groups strongly inhibit agglutination of erythrocytes by influenza virus: The strong inhibition reflects enhances binding through cooperative polyvalent interactions. J Am Chem Soc 1996, 118, 3789–3800, doi:10.1021/ja953729u.
- Makimura, Y; Watanabe, S; Suzuki, T; Suzuki, Y; Ishida, H; Kiso, M; Katayama, T; Kumagai, H; Yamamoto, K. Chemoenzymatic synthesis and application of a sialoglycopolymer with a chitosan backbone as a potent inhibitor of human influenza virus hemagglutination. Carbohydr Res 2006, 341, 1803–1808, doi:10.1016/j.carres.2006.04.024. 16716273
- Choi, S-K; Mammen, M; Whitesides, GM. Generation and in situ evaluation of libraries of poly(acrylic acid) presenting sialosides as side chaina as polyvalent inhibitors of influenza-mediated hemagglutination. J Am Chem Soc 1997, 119, 4103–4111, doi:10.1021/ja963519x.
- Umemura, M; Itoh, M; Makimura, Y; Yamazaki, K; Umekawa, M; Masui, A; Matahira, Y; Shibata, M; Ashida, H; Yamamoto, K. Design of a sialylglycopolymer with a chitosan backbone having efficient inhibitory activity against influenza virus infection. J Med Chem 2008, 51, 4496–4503, doi:10.1021/jm8000967. 18651726
- Totani, K; Kubota, T; Kuroda, T; Murata, T; Hidari, KI-PJ; Suzuki, T; Suzuki, Y; Kobayashi, K; Ashida, H; Yamamoto, K; Usui, T. Chemoenzymatic synthesis and application of glycopolymers containing multivalent sialyloligosaccharides with a poly(L-glutamic acid) backbone for inhibition of infection by influenza viruses. Glycobiology 2003, 13, 315–326, doi:10.1093/glycob/cwg032. 12626382
- Furuike, T; Aiba, S; Suzuki, T; Takahashi, T; Suzuki, Y; Yamada, K; Nishimura, S-I. Synthesis and anti-influenza virus activity of novel glycopolymers having triantennary oligosaccharide branches. J Chem Soc Perkin Trans I 2000, 1, 3000–3005.
- Mammen, M; Dahmann, G; Whitesides, GM. Effective inhibitors of hemagglutination by influenza virus synthesized from polymers having active ester groups. Insight into mechanism of inhibition. J Med Chem 1995, 38, 4179–4190, doi:10.1021/jm00021a007. 7473545
- Reuter, JD; Myc, A; Hayes, MM; Gan, Z; Roy, R; Qin, D; Yin, R; Piehler, LT; Esfand, R; Tomalia, DA; Baker, J, Jr. Inhibition of viral adhesion and infection by sialic-conjugated dendritic polymers. Bioconjug Chem 1999, 10, 271–278, doi:10.1021/bc980099n. 10077477
- Ikeuchi, T; Asaka, T; Saito, M; Tanaka, H; Higuchi, S; Tanaka, K; Saida, K; Uyama, E; Mizusawa, H; Fukuhara, N; Nonaka, I; Takemori, M; Tsuji, S. Gene locus autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome 9. Ann Neurol 1997, 41, 432–437, doi:10.1002/ana.410410405. 9124799
- Eisenberg, I; Avidan, N; Potikha, T; Hochner, H; Chen, M; Olender, T; Barash, M; Shemesh, M; Sadeh, M; Grabov-Nardini, G; et al. The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy. Nat Genet 2001, 29, 83–87, doi:10.1038/ng718. 11528398
- Nishino, I; Noguchi, S; Murayama, K; Driss, A; Sugie, K; Oya, Y; Nagata, T; Chida, K; Takahashi, T; Takusa, Y; et al. Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body pyopathy. Neurology 2002, 59, 1689–1693, doi:10.1212/01.WNL.0000041631.28557.C6. 12473753
- Malicdan, MCV; Noguchi, S; Hayashi, YK; Nonaka, I; Nishino, I. Prophylactic treatment with sialic acid metabolites precludes the development of the myopathic phenotype in the DMRV-hIBM mouse model. Nat Med 2009, 15, 690–695, doi:10.1038/nm.1956. 19448634
|Table 1. The relationship between marine bacteria and enzyme activities.|
|Enzyme origin||Enzyme activities|
|Sialyltransferase activity||Neuraminidase activity|
|Photobacterium phosphoreum JT-ISH-467||α2,3-sialyltransferase||+|
|Photobacterium sp. JT-ISH-224||+|
|Vibrio sp. JT-FAJ-16||−|
|Photobacterium damselae JT0160||α2,6-sialyltransferase||−|
|Photobacterium leiognathi JT-SHIZ-119||+|
|Photobacterium leiognathi JT-SHIZ-145||−|
|Photobacterium sp. JT-ISH-224||−|
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).