Sialic acid O-acetylation: From biosynthesis to roles in health and disease
2021; Elsevier BV; Volume: 297; Issue: 2 Linguagem: Inglês
10.1016/j.jbc.2021.100906
ISSN1083-351X
AutoresEline A. Visser, Sam J. Moons, Suzanne B. P. E. Timmermans, Heleen de Jong, Thomas J. Boltje, Christian Büll,
Tópico(s)Carbohydrate Chemistry and Synthesis
ResumoSialic acids are nine-carbon sugars that frequently cap glycans at the cell surface in cells of vertebrates as well as cells of certain types of invertebrates and bacteria. The nine-carbon backbone of sialic acids can undergo extensive enzymatic modification in nature and O-acetylation at the C-4/7/8/9 position in particular is widely observed. In recent years, the detection and analysis of O-acetylated sialic acids have advanced, and sialic acid-specific O-acetyltransferases (SOATs) and O-acetylesterases (SIAEs) that add and remove O-acetyl groups, respectively, have been identified and characterized in mammalian cells, invertebrates, bacteria, and viruses. These advances now allow us to draw a more complete picture of the biosynthetic pathway of the diverse O-acetylated sialic acids to drive the generation of genetically and biochemically engineered model cell lines and organisms with altered expression of O-acetylated sialic acids for dissection of their roles in glycoprotein stability, development, and immune recognition, as well as discovery of novel functions. Furthermore, a growing number of studies associate sialic acid O-acetylation with cancer, autoimmunity, and infection, providing rationale for the development of selective probes and inhibitors of SOATs and SIAEs. Here, we discuss the current insights into the biosynthesis and biological functions of O-acetylated sialic acids and review the evidence linking this modification to disease. Furthermore, we discuss emerging strategies for the design, synthesis, and potential application of unnatural O-acetylated sialic acids and inhibitors of SOATs and SIAEs that may enable therapeutic targeting of this versatile sialic acid modification. Sialic acids are nine-carbon sugars that frequently cap glycans at the cell surface in cells of vertebrates as well as cells of certain types of invertebrates and bacteria. The nine-carbon backbone of sialic acids can undergo extensive enzymatic modification in nature and O-acetylation at the C-4/7/8/9 position in particular is widely observed. In recent years, the detection and analysis of O-acetylated sialic acids have advanced, and sialic acid-specific O-acetyltransferases (SOATs) and O-acetylesterases (SIAEs) that add and remove O-acetyl groups, respectively, have been identified and characterized in mammalian cells, invertebrates, bacteria, and viruses. These advances now allow us to draw a more complete picture of the biosynthetic pathway of the diverse O-acetylated sialic acids to drive the generation of genetically and biochemically engineered model cell lines and organisms with altered expression of O-acetylated sialic acids for dissection of their roles in glycoprotein stability, development, and immune recognition, as well as discovery of novel functions. Furthermore, a growing number of studies associate sialic acid O-acetylation with cancer, autoimmunity, and infection, providing rationale for the development of selective probes and inhibitors of SOATs and SIAEs. Here, we discuss the current insights into the biosynthesis and biological functions of O-acetylated sialic acids and review the evidence linking this modification to disease. Furthermore, we discuss emerging strategies for the design, synthesis, and potential application of unnatural O-acetylated sialic acids and inhibitors of SOATs and SIAEs that may enable therapeutic targeting of this versatile sialic acid modification. Sugars serve as essential molecular building blocks that can assemble into complex glycans with numerous biological functions (1Marth J.D. A unified vision of the building blocks of life.Nat. Cell Biol. 2008; 10: 1015-1016Crossref PubMed Scopus (0) Google Scholar). Virtually every cell produces glycans; short, long, linear, and branched structures composed of different types of sugar molecules that are attached to membrane and secreted glycoproteins and glycolipids. The vast and diverse collection of glycans produced by a cell or tissue is referred to as “the glycome” (2Schjoldager K.T. Narimatsu Y. Joshi H.J. Clausen H. Global view of human protein glycosylation pathways and functions.Nat. Rev. Mol. Cell Biol. 2020; 21: 729-749Crossref PubMed Scopus (59) Google Scholar). In vertebrate cells, glycans are assembled inside the endoplasmic reticulum, Golgi system, nucleus, cytoplasm, and mitochondria where over 200 glycosyltransferase enzymes build the glycome (2Schjoldager K.T. Narimatsu Y. Joshi H.J. Clausen H. Global view of human protein glycosylation pathways and functions.Nat. Rev. Mol. Cell Biol. 2020; 21: 729-749Crossref PubMed Scopus (59) Google Scholar, 3Narimatsu Y. Joshi H.J. Nason R. Van Coillie J. Karlsson R. Sun L. Ye Z. Chen Y.H. Schjoldager K.T. Steentoft C. Furukawa S. Bensing B.A. Sullam P.M. Thompson A.J. Paulson J.C. et al.An Atlas of human glycosylation pathways enables display of the human glycome by gene engineered cells.Mol. Cell. 2019; 75: 394-407Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar). The glycome regulates a multitude of biological processes, such as the functional and biochemical properties of proteins and lipids, and cellular adhesion, communication, and immune recognition events (4Varki A. Biological roles of glycans.Glycobiology. 2017; 27: 3-49Crossref PubMed Scopus (784) Google Scholar). Important determinants of the biological functions of glycans are the sialic acids (Sias) that reside at the terminal position of glycans in vertebrate cells, some invertebrates, and some human pathogens. The sialic acid family comprises >80 naturally occurring members that are related to the nonulosonic acids, nine-carbon backbone α-keto sugars that are widely found in nature (5Varki A. Schnaar R.L. Schauer R. Sialic acids and other nonulosonic acids.in: Essentials of Glycobiology. 3rd Ed. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY2015: 179-195Google Scholar, 6Schauer R. Kamerling J.P. Exploration of the sialic acid world.Adv. Carbohydr. Chem. Biochem. 2018; 75: 1-213Crossref PubMed Scopus (67) Google Scholar, 7Angata T. Varki A. Chemical diversity in the sialic acids and related alpha-keto acids: An evolutionary perspective.Chem. Rev. 2002; 102: 439-469Crossref PubMed Scopus (974) Google Scholar). Regarding this large diversity, the assembly of sialic acid-carrying glycans (sialoglycans) forms a subclass within the glycome—the sialome (8Cohen M. Varki A. The sialome--far more than the sum of its parts.OMICS. 2010; 14: 455-464Crossref PubMed Scopus (0) Google Scholar). The diverse biological functions of sialic acids include protection of the cell surface and glycoproteins from proteases (9Aquino D. Wong R. Margolis R.U. Margolis R.K. Sialic acid residues inhibit proteolytic degradation of dopamine beta-hydroxylase.FEBS Lett. 1980; 112: 195-198Crossref PubMed Scopus (0) Google Scholar, 10Gorog P. Pearson J.D. Sialic acid moieties on surface glycoproteins protect endothelial cells from proteolytic damage.J. Pathol. 1985; 146: 205-212Crossref PubMed Google Scholar); regulation of serum half-life of glycoproteins and erythrocytes that are cleared in the liver upon desialylation (11Morell A.G. Gregoriadis G. Scheinberg I.H. Hickman J. Ashwell G. The role of sialic acid in determining the survival of glycoproteins in the circulation.J. Biol. Chem. 1971; 246: 1461-1467Abstract Full Text PDF PubMed Google Scholar, 12Sorensen A.L. Rumjantseva V. Nayeb-Hashemi S. Clausen H. Hartwig J.H. Wandall H.H. Hoffmeister K.M. Role of sialic acid for platelet life span: Exposure of beta-galactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor-expressing liver macrophages and hepatocytes.Blood. 2009; 114: 1645-1654Crossref PubMed Scopus (137) Google Scholar, 13Yang W.H. Aziz P.V. Heithoff D.M. Mahan M.J. Smith J.W. Marth J.D. An intrinsic mechanism of secreted protein aging and turnover.Proc. Natl. Acad. Sci. U. S. A. 2015; 112: 13657-13662Crossref PubMed Scopus (60) Google Scholar); and likely formation of the blood vessel lumen (14Strilic B. Eglinger J. Krieg M. Zeeb M. Axnick J. Babal P. Muller D.J. Lammert E. Electrostatic cell-surface repulsion initiates lumen formation in developing blood vessels.Curr. Biol. 2010; 20: 2003-2009Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). In the immune system, sialoglycans such as sialyl Lewisx contribute to immune cell trafficking via binding to selectins on the endothelium (15McEver R.P. Moore K.L. Cummings R.D. Leukocyte trafficking mediated by selectin-carbohydrate interactions.J. Biol. Chem. 1995; 270: 11025-11028Abstract Full Text Full Text PDF PubMed Scopus (574) Google Scholar), and they form the ligands for the immunomodulatory Siglec receptors that set the threshold for immune activation (16Macauley M.S. Crocker P.R. Paulson J.C. Siglec-mediated regulation of immune cell function in disease.Nat. Rev. Immunol. 2014; 14: 653-666Crossref PubMed Scopus (466) Google Scholar, 17Büll C. Heise T. Adema G.J. Boltje T.J. Sialic acid mimetics to target the sialic acid-siglec Axis.Trends Biochem. Sci. 2016; 41: 519-531Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar). Sialic acids also serve as binding sites for human pathogens and can be utilized by microorganisms for molecular mimicry (18Heise T. Langereis J.D. Rossing E. de Jonge M.I. Adema G.J. Büll C. Boltje T.J. Selective inhibition of sialic acid-based molecular mimicry in Haemophilus influenzae abrogates serum resistance.Cell Chem. Biol. 2018; 25: 1279-1285.e1278Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 19Stencel-Baerenwald J.E. Reiss K. Reiter D.M. Stehle T. Dermody T.S. The sweet spot: Defining virus-sialic acid interactions.Nat. Rev. Microbiol. 2014; 12: 739-749Crossref PubMed Scopus (168) Google Scholar). Furthermore, aberrant sialoglycan expression is associated with tumor growth, immune evasion, and metastasis (20Büll C. Stoel M.A. den Brok M.H. Adema G.J. Sialic acids sweeten a tumor's life.Cancer Res. 2014; 74: 3199-3204Crossref PubMed Scopus (220) Google Scholar, 21van de Wall S. Santegoets K.C.M. van Houtum E.J.H. Büll C. Adema G.J. Sialoglycans and Siglecs can shape the tumor immune microenvironment.Trends Immunol. 2020; 41: 274-285Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar, 22Pearce O.M. Laubli H. Sialic acids in cancer biology and immunity.Glycobiology. 2016; 26: 111-128Crossref PubMed Scopus (192) Google Scholar). The biological versatility of sialic acids is reflected in their large structural diversity that arises from the natural modifications (Fig. 1A) and the different linkages (α2-3/6/8) to underlying glycans and glycoconjugates (N-/O-glycans, glycolipids). The most prevalent sialic acid derivative in humans is N-acetylneuraminic acid (Neu5Ac), and other notable sialic acid derivatives are 2-keto-3-deoxynononic acid (KDN) and N-glycolylneuraminic acid (Neu5Gc) (5Varki A. Schnaar R.L. Schauer R. Sialic acids and other nonulosonic acids.in: Essentials of Glycobiology. 3rd Ed. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY2015: 179-195Google Scholar). Interestingly, humans have lost the ability to biosynthesize Neu5Gc due to a mutation in the CMP-Neu5Ac hydroxylase (CMAH) gene (23Chou H.H. Takematsu H. Diaz S. Iber J. Nickerson E. Wright K.L. Muchmore E.A. Nelson D.L. Warren S.T. Varki A. A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence.Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 11751-11756Crossref PubMed Scopus (411) Google Scholar); however, Neu5Gc can be scavenged from exogenous, dietary sources, and low amounts of this derivative are incorporated into the sialoglycans of human cells (24Tangvoranuntakul P. Gagneux P. Diaz S. Bardor M. Varki N. Varki A. Muchmore E. Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid.Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 12045-12050Crossref PubMed Scopus (434) Google Scholar). Further modifications at any of the hydroxyl or amine groups of the sialic acid backbone result in the >80 distinct naturally occurring sialic acid types known to date (6Schauer R. Kamerling J.P. Exploration of the sialic acid world.Adv. Carbohydr. Chem. Biochem. 2018; 75: 1-213Crossref PubMed Scopus (67) Google Scholar, 7Angata T. Varki A. Chemical diversity in the sialic acids and related alpha-keto acids: An evolutionary perspective.Chem. Rev. 2002; 102: 439-469Crossref PubMed Scopus (974) Google Scholar). Analysis of these sialic acid types in biological samples is challenging, and often their biosynthesis and biological functions are not fully understood. Presumably, the extensive Sia modifications may be the result of an evolutionary race between the host and pathogens that exploit sialoglycans for infection. In line with the Red Queen hypothesis, an evolutionary biology concept in which the host species must constantly adapt to survive competition with evolving pathogens, Sia modifications may have evolved to abrogate pathogen interactions while preserving overall endogenous functions in the host (25Varki A. Nothing in glycobiology makes sense, except in the light of evolution.Cell. 2006; 126: 841-845Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar). Moreover, the modifications may contribute additional regulatory or informational cues to sialoglycan recognition that are advantageous to the host. A common natural sialic acid modification is the addition of one or more O-acetyl esters to the hydroxyl groups of sialic acid residues yielding about 20 different naturally occurring O-Ac-Sias (26Mandal C. Schwartz-Albiez R. Vlasak R. Functions and biosynthesis of O-acetylated sialic acids.Top. Curr. Chem. 2015; 366: 1-30PubMed Google Scholar). Due to advances in the detection and analysis of O-Ac-Sias and the identification of SOATs and SIAEs in mammalian cells, invertebrates, bacteria, and viruses, many aspects regarding the biosynthesis and roles in biology and disease of this modification have recently been uncovered, and we anticipate that this rapid pace of discovery will continue. Here, we review the current understanding of the biosynthesis of O-acetylated sialic acids and their roles in health and disease and discuss implications for the design, synthesis, and emerging applications of sialic acid O-acetylation inhibitors. Soon after the discovery of sialic acids by Blix and Klenk (27Blix G. Über die Kohlenhydratgruppen des Submaxillarismucins.Z. Physiol. Chem. 1936; 240: 43-54Crossref Google Scholar, 28Klenk E. Neuraminsäure, das Spaltprodukt eines neuen Gehirnlipoids.Z. Physiol. Chem. 1941; 268: 50-58Crossref Google Scholar), the presence of O-acetyl modifications was noted, and among others, Schauer and Kamerling succeeded in their verification using mass spectrometry (6Schauer R. Kamerling J.P. Exploration of the sialic acid world.Adv. Carbohydr. Chem. Biochem. 2018; 75: 1-213Crossref PubMed Scopus (67) Google Scholar, 29Kamerling J.P. Vliegenthart J.F. Identification of O-cetylated N-acylneuraminic acids by mass spectrometry.Carbohydr. Res. 1975; 41: 7-17Crossref PubMed Scopus (0) Google Scholar). O-acetylation can occur at the C-4, C-7, C-8, and C-9 hydroxyl groups of the nonulosonic acid and sialic acid backbone (Fig. 1A). These modifications are denoted as exemplified for Neu5Ac (which carries an N-acetyl group at C-5) as Neu4,5Ac2, Neu5,7Ac2, Neu5,8Ac2, and Neu5,9Ac2, respectively (30Varki A. Cummings R.D. Aebi M. Packer N.H. Seeberger P.H. Esko J.D. Stanley P. Hart G. Darvill A. Kinoshita T. Prestegard J.J. Schnaar R.L. Freeze H.H. Marth J.D. Bertozzi C.R. et al.Symbol nomenclature for graphical representations of glycans.Glycobiology. 2015; 25: 1323-1324Crossref PubMed Scopus (448) Google Scholar). O-acetylation can also occur simultaneously at multiple positions, giving rise to di- and tri-O-acetylated Sias such as Neu5,7,9Ac3 or Neu5,7,8,9Ac4, respectively. An overview of the identified naturally occurring O-Ac-Sias is provided by Varki, Schauer, and Kamerling, who made seminal contributions to their identification and biology (6Schauer R. Kamerling J.P. Exploration of the sialic acid world.Adv. Carbohydr. Chem. Biochem. 2018; 75: 1-213Crossref PubMed Scopus (67) Google Scholar, 7Angata T. Varki A. Chemical diversity in the sialic acids and related alpha-keto acids: An evolutionary perspective.Chem. Rev. 2002; 102: 439-469Crossref PubMed Scopus (974) Google Scholar, 31Varki A. Roland Schauer (1936-2019): A tribute to “Mr. Sialic acid”.Glycobiology. 2020; 30: 132-133Crossref Google Scholar). O-acetylation is not static, as spontaneous migration of the O-acetyl groups over the glycerol chain can occur, but not to or from the C-4 position (32Kamerling J.P. Schauer R. Shukla A.K. Stoll S. Van Halbeek H. Vliegenthart J.F. Migration of O-acetyl groups in N,O-acetylneuraminic acids.Eur. J. Biochem. 1987; 162: 601-607Crossref PubMed Google Scholar). At neutral and slightly basic pH, bidirectional O-acetyl group migration along the glycerol tail from C-7, C-8, and C-9 was observed yielding Neu5,7Ac2, Neu5,8Ac2, and Neu5,9Ac2, respectively (32Kamerling J.P. Schauer R. Shukla A.K. Stoll S. Van Halbeek H. Vliegenthart J.F. Migration of O-acetyl groups in N,O-acetylneuraminic acids.Eur. J. Biochem. 1987; 162: 601-607Crossref PubMed Google Scholar, 33Ji Y. Sasmal A. Li W. Oh L. Srivastava S. Hargett A.A. Wasik B.R. Yu H. Diaz S. Choudhury B. Parrish C.R. Freedberg D.I. Wang L.P. Varki A. Chen X. Reversible O-acetyl migration within the sialic acid side chain and its influence on protein recognition.ACS Chem. Biol. 2021; https://doi.org/10.1021/acschembio.0c00998Crossref PubMed Scopus (1) Google Scholar). In addition, the formation of di-O-acetyl-Sia Neu5,8,9Ac3 from Neu5,7,9Ac3 has been indicated (32Kamerling J.P. Schauer R. Shukla A.K. Stoll S. Van Halbeek H. Vliegenthart J.F. Migration of O-acetyl groups in N,O-acetylneuraminic acids.Eur. J. Biochem. 1987; 162: 601-607Crossref PubMed Google Scholar, 34Varki A. Diaz S. The release and purification of sialic acids from glycoconjugates: Methods to minimize the loss and migration of O-acetyl groups.Anal. Biochem. 1984; 137: 236-247Crossref PubMed Google Scholar). Sia O-acetyl group migration can be bidirectional and proceeds intramolecularly through orthoester intermediates, which mainly takes place at neutral and mild basic pH while it stabilizes at mildly acidic pH <5 (32Kamerling J.P. Schauer R. Shukla A.K. Stoll S. Van Halbeek H. Vliegenthart J.F. Migration of O-acetyl groups in N,O-acetylneuraminic acids.Eur. J. Biochem. 1987; 162: 601-607Crossref PubMed Google Scholar, 33Ji Y. Sasmal A. Li W. Oh L. Srivastava S. Hargett A.A. Wasik B.R. Yu H. Diaz S. Choudhury B. Parrish C.R. Freedberg D.I. Wang L.P. Varki A. Chen X. Reversible O-acetyl migration within the sialic acid side chain and its influence on protein recognition.ACS Chem. Biol. 2021; https://doi.org/10.1021/acschembio.0c00998Crossref PubMed Scopus (1) Google Scholar). Recent advances in sample preparation and analysis of O-Ac-Sia species now provide opportunity to address the migration process of the acetyl group (35Wu Z. Li H. Zhang Q. Liu X. Zheng Q. Li J. Characterization of O-acetylation in sialoglycans by MALDI-MS using a combination of methylamidation and permethylation.Sci. Rep. 2017; 7: 46206Crossref PubMed Scopus (10) Google Scholar, 36Khedri Z. Xiao A. Yu H. Landig C.S. Li W. Diaz S. Wasik B.R. Parrish C.R. Wang L.P. Varki A. Chen X. A chemical biology solution to problems with studying biologically important but unstable 9-O-acetyl sialic acids.ACS Chem. Biol. 2017; 12: 214-224Crossref PubMed Scopus (0) Google Scholar, 37Li W. Battistel M.D. Reeves H. Oh L. Yu H. Chen X. Wang L.P. Freedberg D.I. A combined NMR, MD and DFT conformational analysis of 9-O-acetyl sialic acid-containing GM3 ganglioside glycan and its 9-N-acetyl mimic.Glycobiology. 2020; 30: 787-801Crossref PubMed Scopus (0) Google Scholar). The biosynthesis of O-Ac-Sias in mammalian cells starts with sialic acids that are produced de novo in the cytoplasm via several enzymatic steps or derived from exogenous sources (e.g., dietary) (38Freeze H.H. Hart G.W. Schnaar R.L. Glycosylation precursors.in: Essentials of Glycobiology. 3rd Ed. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY2015: 51-63Google Scholar, 39Moons S.J. Adema G.J. Derks M.T. Boltje T.J. Büll C. Sialic acid glycoengineering using N-acetylmannosamine and sialic acid analogs.Glycobiology. 2019; 29: 433-445PubMed Google Scholar). Sialic acids are activated in the nucleus by conjugation to cytidine 5′-monophosphate (CMP) and transported into the Golgi system where 20 sialyltransferase isoenzymes use CMP-sialic acids as donor to incorporate sialic acids into glycans via distinct glycosidic linkages (α2-3/6/8) (2Schjoldager K.T. Narimatsu Y. Joshi H.J. Clausen H. Global view of human protein glycosylation pathways and functions.Nat. Rev. Mol. Cell Biol. 2020; 21: 729-749Crossref PubMed Scopus (59) Google Scholar, 40Harduin-Lepers A. Vallejo-Ruiz V. Krzewinski-Recchi M.A. Samyn-Petit B. Julien S. Delannoy P. The human sialyltransferase family.Biochimie. 2001; 83: 727-737Crossref PubMed Scopus (402) Google Scholar). O-acetylation takes place in the Golgi system and involves the activity of sialic acid O-acetyltransferases (SOATs) and sialic acid esterases (SIAEs) that add and remove O-acetyl groups on sialic acids, respectively (26Mandal C. Schwartz-Albiez R. Vlasak R. Functions and biosynthesis of O-acetylated sialic acids.Top. Curr. Chem. 2015; 366: 1-30PubMed Google Scholar) (Fig. 1B). So far, a single mammalian SOAT (CASD1, capsule structure1 domain containing 1) has been identified (41Arming S. Wipfler D. Mayr J. Merling A. Vilas U. Schauer R. Schwartz-Albiez R. Vlasak R. The human Cas1 protein: A sialic acid-specific O-acetyltransferase?.Glycobiology. 2011; 21: 553-564Crossref PubMed Scopus (40) Google Scholar, 42Baumann A.M. Bakkers M.J. Buettner F.F. Hartmann M. Grove M. Langereis M.A. de Groot R.J. Muhlenhoff M. 9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate.Nat. Commun. 2015; 6: 7673Crossref PubMed Google Scholar), and one sialic-acid-specific esterase (SIAE) is known (43Guimaraes M.J. Bazan J.F. Castagnola J. Diaz S. Copeland N.G. Gilbert D.J. Jenkins N.A. Varki A. Zlotnik A. Molecular cloning and characterization of lysosomal sialic acid O-acetylesterase.J. Biol. Chem. 1996; 271: 13697-13705Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 44Orizio F. Damiati E. Giacopuzzi E. Benaglia G. Pianta S. Schauer R. Schwartz-Albiez R. Borsani G. Bresciani R. Monti E. Human sialic acid acetyl esterase: Towards a better understanding of a puzzling enzyme.Glycobiology. 2015; 25: 992-1006Crossref PubMed Scopus (8) Google Scholar, 45Takematsu H. Diaz S. Stoddart A. Zhang Y. Varki A. Lysosomal and cytosolic sialic acid 9-O-acetylesterase activities can Be encoded by one gene via differential usage of a signal peptide-encoding exon at the N terminus.J. Biol. Chem. 1999; 274: 25623-25631Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 46Stoddart A. Zhang Y. Paige C.J. Molecular cloning of the cDNA encoding a murine sialic acid-specific 9-O-acetylesterase and RNA expression in cells of hematopoietic and non-hematopoietic origin.Nucleic Acids Res. 1996; 24: 4003-4008Crossref PubMed Scopus (0) Google Scholar, 47Butor C. Higa H.H. Varki A. Structural, immunological, and biosynthetic studies of a sialic acid-specific O-acetylesterase from rat liver.J. Biol. Chem. 1993; 268: 10207-10213Abstract Full Text PDF PubMed Google Scholar) (Table 1). Especially the identification of CASD1 remained challenging for several decades due to lability of the intact enzyme during purification (48Butor C. Diaz S. Varki A. High level O-acetylation of sialic acids on N-linked oligosaccharides of rat liver membranes. Differential subcellular distribution of 7- and 9-O-acetyl groups and of enzymes involved in their regulation.J. Biol. Chem. 1993; 268: 10197-10206Abstract Full Text PDF PubMed Google Scholar, 49Lrhorfi L.A. Srinivasan G.V. Schauer R. Properties and partial purification of sialate-O-acetyltransferase from bovine submandibular glands.Biol. Chem. 2007; 388: 297-306Crossref PubMed Scopus (0) Google Scholar, 50Ogura K. Nara K. Watanabe Y. Kohno K. Tai T. Sanai Y. Cloning and expression of cDNA for O-acetylation of GD3 ganglioside.Biochem. Biophys. Res. Commun. 1996; 225: 932-938Crossref PubMed Scopus (67) Google Scholar, 51Kanamori A. Nakayama J. Fukuda M.N. Stallcup W.B. Sasaki K. Fukuda M. Hirabayashi Y. Expression cloning and characterization of a cDNA encoding a novel membrane protein required for the formation of O-acetylated ganglioside: A putative acetyl-CoA transporter.Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 2897-2902Crossref PubMed Scopus (0) Google Scholar, 52Shi W.X. Chammas R. Varki A. Induction of sialic acid 9-O-acetylation by diverse gene products: Implications for the expression cloning of sialic acid O-acetyltransferases.Glycobiology. 1998; 8: 199-205Crossref PubMed Scopus (0) Google Scholar). Eventually, mammalian SIAE was cloned in 1996 (43Guimaraes M.J. Bazan J.F. Castagnola J. Diaz S. Copeland N.G. Gilbert D.J. Jenkins N.A. Varki A. Zlotnik A. Molecular cloning and characterization of lysosomal sialic acid O-acetylesterase.J. Biol. Chem. 1996; 271: 13697-13705Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar), whereas CASD1 was identified 2011 through data mining of the human genome for acetyltransferase genes with unknown functions (41Arming S. Wipfler D. Mayr J. Merling A. Vilas U. Schauer R. Schwartz-Albiez R. Vlasak R. The human Cas1 protein: A sialic acid-specific O-acetyltransferase?.Glycobiology. 2011; 21: 553-564Crossref PubMed Scopus (40) Google Scholar) and biochemically characterized in 2015 (42Baumann A.M. Bakkers M.J. Buettner F.F. Hartmann M. Grove M. Langereis M.A. de Groot R.J. Muhlenhoff M. 9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate.Nat. Commun. 2015; 6: 7673Crossref PubMed Google Scholar).Table 1Occurrence of O-Ac-Sias and biosynthetic enzymes in humans and microorganismsSpeciesO-Ac-Sia formSOATSIAEO-Ac-Sia GBPReferencesHomo sapiensDiverse (Fig. 1C)CASD1SIAEnd(41Arming S. Wipfler D. Mayr J. Merling A. Vilas U. Schauer R. Schwartz-Albiez R. Vlasak R. The human Cas1 protein: A sialic acid-specific O-acetyltransferase?.Glycobiology. 2011; 21: 553-564Crossref PubMed Scopus (40) Google Scholar, 42Baumann A.M. Bakkers M.J. Buettner F.F. Hartmann M. Grove M. Langereis M.A. de Groot R.J. Muhlenhoff M. 9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate.Nat. Commun. 2015; 6: 7673Crossref PubMed Google Scholar, 43Guimaraes M.J. Bazan J.F. Castagnola J. Diaz S. Copeland N.G. Gilbert D.J. Jenkins N.A. Varki A. Zlotnik A. Molecular cloning and characterization of lysosomal sialic acid O-acetylesterase.J. Biol. Chem. 1996; 271: 13697-13705Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 44Orizio F. Damiati E. Giacopuzzi E. Benaglia G. Pianta S. Schauer R. Schwartz-Albiez R. Borsani G. Bresciani R. Monti E. Human sialic acid acetyl esterase: Towards a better understanding of a puzzling enzyme.Glycobiology. 2015; 25: 992-1006Crossref PubMed Scopus (8) Google Scholar)Campylobacter jejuniNeu5,9Ac2 (α2-8-linked)aCapsular O-Ac-Sia.Orf11ndnd(190Houliston R.S. Endtz H.P. Yuki N. Li J. Jarrell H.C. Koga M. van Belkum A. Karwaski M.F. Wakarchuk W.W. Gilbert M. Identification of a sialate O-acetyltransferase from Campylobacter jejuni: Demonstration of direct transfer to the C-9 position of terminalalpha-2, 8-linked sialic acid.J. Biol. Chem. 2006; 281: 11480-11486Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar)Escherichia coli K1Neu5,7/9Ac2 (α2-3/8-linked)aCapsular O-Ac-Sia.NeuO NeuDNeuAnd(194Higa H.H. Varki A. Acetyl-coenzyme A:polysialic acid O-acetyltransferase from K1-positive Escherichia coli. The enzyme responsible for the O-acetyl plus phenotype and for O-acetyl form variation.J. Biol. Chem. 1988; 263: 8872-8878Abstract Full Text PDF PubMed Google Scholar, 195Deszo E.L. Steenbergen S.M. Freedberg D.I. Vimr E.R. Escherichia coli K1 polysialic acid O-acetyltransferase gene, neuO, and the mechanism of capsule form variation involving a mobile contingency locus.Proc. Natl. Acad. Sci. U. S. A. 2005; 102: 5564-5569Crossref PubMed Scopus (60) Google Scholar, 196Schulz E.C. Bergfeld A.K. Ficner R. Muhlenhoff M. Crystal structure analysis of the polysialic acid specific O-acetyltransferase NeuO.PLoS One. 2011; 6e17403Crossref PubMed Scopus (11) Google Scholar, 197Bergfeld A.K. Claus H. Vogel U. Mühlenhoff M. Biochemical characterization of thepolysialic acid-specific O-acetyltransferase NeuO of Escherichia coli K1.J. Biol. Chem. 2007; 282: 22217-22227Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 198Steenbergen S.M. Lee Y.C. Vann W.F. Vionnet J. Wright L.F. Vimr E.R. Separate pathways for O acetylation of polymeric and monomeric sialic acids and identification of sialyl O-acetyl esterase in Escherichia coli K1.J. Bacteriol. 2006; 188: 6195-6206Crossref PubMed Scopus (51) Google Scholar)Enterohemorrhagic E. coli (EHEC)Neu5,9Ac2NANanS NanS-pnd(167Feuerbaum S. Saile N. Pohlentz G. Muthing J. Schmidt H. De-O-Acetylation of mucin-derived sialic acids by recombinant NanS-p esterases of Escherichia coli O157:H7 strain EDL933.Int. J. Med. Microbiol. 2018; 308: 1113-1120Crossref PubMed Scopus (5) Google Scholar, 168Saile N. Schwarz L. Eissenberger K. Klumpp J. Fricke F.W. Schmidt H. Growth advantage of Escherichia coli O104:H4 strains on 5-N-acetyl-9-O-acetyl neuraminic acid as a carbon source is dependent on heterogeneous phage-Borne nanS-p esterases.Int. J. Med. Microbiol. 2018; 308: 459-468Crossref PubMed Scopus (6) Google Scholar, 169Rangara
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