Cloning, expression, and characterization of sialic acid synthases

Hao, Jijun; Balagurumoorthy, Pichumani; Sarilla, Suryakala; Sundaramoorthy, Munirathinam

doi:10.1016/j.bbrc.2005.10.113

Cited by 33 publications

(19 citation statements)

References 30 publications

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“…In contrast to bacterial NulO biosynthetic pathways that synthesize Neu5Ac from ManNAc (N-acetyl mannosamine), the mammalian pathway relies on a NulO synthase with unique specificity for 6-phosphate-modified ManNAc, to generate 9-phosphate-modified Neu5Ac [22]. A set of adapter enzymes precede (kinase) and follow (phosphatase) the NulO synthase in the animal pathway (see Figure 7).…”

Section: Resultsmentioning

confidence: 99%

Expression of sialic acids and other nonulosonic acids in Leptospira

et al. 2012

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BackgroundSialic acids are negatively charged nine carbon backbone sugars expressed on mammalian cell surfaces. Sialic acids are part of a larger family of nonulosonic acid (NulO) molecules that includes pseudaminic and legionaminic acids. Microbial expression of sialic acids and other nonulosonic acids has been shown to contribute to host-microbe interactions in a variety of contexts, including participation in colonization, immune subversion, and behaviors such as biofilm formation, autoagglutination and motility. Previous research has suggested that some spirochetes may also express these molecules.ResultsHere we use a combination of molecular tools to investigate the presence of NulO biosynthetic gene clusters among clinical and saprophytic isolates of the genus Leptospira. Polymerase chain reaction and Southern blotting suggested that a variety of leptospires encoded NulO biosynthetic pathways. High performance liquid chromatography and mass spectrometry analyses provided biochemical evidence that di-N-acetylated NulO molecules are expressed at relatively high levels by L. interrogans serovar Lai strain 55601, and at lower levels by L. alexanderi serovar Manhao and L. fainei serovar Hurstbridge. Endogenous expression of N-acetylneuraminic acid (Neu5Ac, the most common sialic acid) was documented in L. interrogans serovar Copenhageni strain L1-130. Neu5Ac biosynthesis is also supported by a unique gene fusion event resulting in an enzyme with an N-terminal N-acetylneuraminic acid synthase domain and a C-terminal phosphatase domain. This gene fusion suggests that L. interrogans uses a Neu5Ac biosynthetic pathway more similar to animals than to other bacteria. Analysis of the composition and phylogeny of putative NulO biosynthetic gene clusters in L. interrogans serovar Lai and serovar Copenhageni revealed that both strains have complete biosynthetic pathways for legionamimic acid synthesis, a molecule with the same stereochemistry as sialic acid. Lectin-based affinity purification of NulO-modified molecules, followed by mass spectrometric identification suggests post-translational modification of surface lipoproteins, including Loa22.ConclusionsLeptospira species encode NulO biosynthetic pathways and synthesize multiple NulO molecules including sialic acid. Additional studies are needed to clarify the exact context and functional significance of NulO expression. These findings have implications for immune evasion during systemic leptospirosis.

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Section: Resultsmentioning

confidence: 99%

Expression of sialic acids and other nonulosonic acids in Leptospira

et al. 2012

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“…The catalytic efficiency of BT1714 is low but consistent with that reported for the human Neu5NAc-9-P synthase (for reaction with NAc-mannose-2-amine 6-phosphate k cat = 1.3 min −1 and K m = 1.0 mM; for reaction with mannose 6-phosphate k cat = 0.6 min −1 and K m = 2.6 mM). BT1714 differs from the human Neu5NAc-9P synthase in that it recognizes only mannose-6-phosphate as substrate, whereas the human Neu5NAc-9P synthase shows a small preference for NAc-mannose-2-amine 6-phosphate over mannose 6-phosphate (Hao et al, 2005). …”

Section: Resultsmentioning

confidence: 99%

Human Symbiont Bacteroides thetaiotaomicron Synthesizes 2-Keto-3-Deoxy-D-Glycero-D- Galacto-Nononic Acid (KDN)

Wang

Allen

et al. 2008

Chemistry & Biology

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Summary The proper functioning of the human intestine is dependent on its bacterial symbionts, the most predominant of which belong to the Phylum Bacteroidetes. These bacteria are known to use variable displays of multiple capsular polysaccharides (CPs) to aid in their survival and foraging within the intestine. Bacteroides thetaiotaomicron, is a prominent human gut symbiont and a remarkably versatile glycophile. The structure determination of the CPs encoded by the eight CP loci is the key to understanding the mechanism of this organism’s adaptation on a molecular level. Herein, we report the bioinformatics based discovery and chemical demonstration of a novel biosynthetic pathway that forms and cytidylates 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN), most likely for inclusion in the CP encoded by B. thetaiotaomicron CP locus 7.

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“…Because archaea are not known to incorporate sialic acid into their glycans but have been shown to use homologous biosynthetic pathways for the incorporation of the related nonulosonic acids (NulOs), legionaminic acid and pseudaminic acid (30,31), it is possible that GT97 glycosyltransferases exhibit specificity for these CMP-activated sugars. Supporting the putative function of GT97 family members as NulO transferases, the genome sequences of all of the identified organisms were found to harbor homologs of other nonulosonic acid biosynthesis genes, specifically NulO synthases (32,30) and CMPNulO synthetase (33,30). Although the role of sialylated structures in commensal organisms and opportunistic pathogens is generally understood to be the avoidance of the immune system by molecular mimicry of host structures (34), the functional significance of GT97 family proteins in extreme halophiles is less clear.…”

Section: Volume 289 • Number 49 • December 5 2014mentioning

confidence: 93%

Dissection of Hexosyl- and Sialyltransferase Domains in the Bifunctional Capsule Polymerases from Neisseria meningitidis W and Y Defines a New Sialyltransferase Family

Romanow

Keys

Stummeyer

et al. 2014

Journal of Biological Chemistry

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Background: Capsule polymerases of Neisseria meningitidis serogroups W and Y comprise hexosyl-and sialyltransferase activity. Results: Hexosyltransferase activity is encoded by the predicted N-terminal GT-B fold. Sialyltransferase activity requires 168 additional amino acids upstream of the predicted C-terminal GT-B fold. Conclusion:The sialyltransferase domains of NmW/Y define a new glycosyltransferase (CAZy) family. Significance: The new CAZy family comprises sequences from distantly related species.

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Cloning, expression, and characterization of sialic acid synthases

Cited by 33 publications

References 30 publications

Expression of sialic acids and other nonulosonic acids in Leptospira

Expression of sialic acids and other nonulosonic acids in Leptospira

Human Symbiont Bacteroides thetaiotaomicron Synthesizes 2-Keto-3-Deoxy-D-Glycero-D- Galacto-Nononic Acid (KDN)

Dissection of Hexosyl- and Sialyltransferase Domains in the Bifunctional Capsule Polymerases from Neisseria meningitidis W and Y Defines a New Sialyltransferase Family

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