Metabolic Fate of Unsaturated Glucuronic/Iduronic Acids from Glycosaminoglycans

Maruyama, Yukie; Oiki, Shigetoshi; Takase, Ryuichi; Mikami, Bunzo; Murata, Kousaku; Hashimoto, Wataru

doi:10.1074/jbc.m114.604546

Cited by 22 publications

(18 citation statements)

References 50 publications

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“…α-Keto acid DHU non-enzymatically produced from unsaturated uronic acids from GAGs is converted to 3-deoxy-d- glycero -2,5-hexodiulosonic acid (DK-II) by DhuI 9 . The resultant product is reduced to 2-keto-3-deoxy-d-gluconic acid (KDG) by NADH-dependent DhuD.…”

Section: Resultsmentioning

confidence: 99%

“…1C,D , the GAG cluster of Lactobacillus encodes KduI and KduD in place of streptococcal isomerase DhuI and reductase DhuD. Due to a lack of the hydroxyl group at C4 position, unsaturated glucuronic and iduronic acids generated from GAGs are identical to unsaturated galacturonic acid 9 , suggesting that the Lactobacillus KduI and KduD correspond to streptococcal GAG-metabolising DhuI and DhuD, respectively, although there is little sequence similarity between KduI and DhuI and between KduD and DhuD. Enzyme characterisation of the recombinant Lactobacillus KduI and KduD indicated that 4-deoxy-l- threo -5-hexosulose-uronate ketol-isomerase KduI catalyses the isomerase reaction from DHU to DK-II, which is further reduced to KDG by NADH-dependent reductase KduD.…”

Section: Discussionmentioning

confidence: 99%

“…In the case of Streptococcus , hyaluronan is depolymerised to an unsaturated disaccharide with a double bond in C4–C5 at the non-reducing terminus by cell-surface hyaluronate lyase (HysA) through a β-elimination reaction 5 . Our previous reports demonstrated that the resultant unsaturated disaccharide was degraded into two constituent monosaccharides (unsaturated glucuronic acid and N -acetyl-d-glucosamine) by cytoplasmic unsaturated glucuronyl hydrolase (UGL) 8 , and that 4-deoxy-l- threo -5-hexosulose-uronic acid (α-keto acid, DHU) non-enzymatically converted from unsaturated glucuronic acid was metabolised to pyruvate and glyceraldehyde-3-phosphate by consecutive reactions of isomerase (DhuI), NADH-dependent reductase (DhuD), kinase (KdgK), and aldolase (KdgA) 9 . These enzymes (HysA, UGL, DhuI, DhuD, KdgK, and KdgA) for depolymerisation, degradation and metabolism of GAGs are coded in a GAG genetic cluster (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…1B ). Two genes for isomerase KduI and reductase KduD responsible for pectin metabolism 11 are also included in the GAG cluster, and KduI and KduD seem to correspond to DhuI and DhuD, respectively 9 , although the action of KduI and KduD toward GAG-derived products remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Probiotics in human gut microbiota can degrade host glycosaminoglycans

Kawai

Kamochi

Oiki

et al. 2018

Sci Rep

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Glycosaminoglycans (GAGs) (e.g. heparin, chondroitin sulfate, and hyaluronan) show various significant physiological functions as a major component of extracellular matrix in animals. Some bacteria target GAGs for adhesion and/or infection to host cells, although no probiotics have been known to degrade GAGs. Here, we show GAG degradation by probiotics from human gut microbiota and their adhesion to human intestinal cells through a GAG. GAG-degrading bacteria were isolated from human faeces and identified as Enterococcus faecium, and some typical probiotics such as Lactobacillus casei, Lactobacillus rhamnosus and Enterococcus faecalis were also found to degrade heparin. GAG-degrading lactobacilli and enterococci including the isolated E. faecium possessed a genetic cluster encoding GAG-degrading/metabolising enzymes in the bacterial genome. KduI and KduD enzymes encoded in the GAG cluster of L. rhamnosus functioned as 4-deoxy-l-threo-5-hexosulose-uronate ketol-isomerase and 2-keto-3-deoxy-d-gluconate dehydrogenase, respectively, both of which were crucial for GAG metabolism. GAG-degrading L. rhamnosus and E. faecium attached to human intestinal Caco-2 cells via heparin. Some species of Bacteroides, considered to be the next generation probiotics, degraded chondroitin sulfate C and hyaluronan, and genes coding for the Bacteroides GAG-degrading enzyme were frequently detected from human gut microbiota. This is the first report on GAG-degrading probiotics in human gut microbiota.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Probiotics in human gut microbiota can degrade host glycosaminoglycans

Kawai

Kamochi

Oiki

et al. 2018

Sci Rep

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“…Metabolic enzymes, i.e. isomerase, NADH-dependent reductase, kinase, and aldolase, subsequently metabolize the unsaturated uronate to pyruvate and glyceraldehyde-3-phosphate 7 . The genes encoding these enzymes that are essential for depolymerization, degradation, and metabolism of GAGs assemble a cluster in the bacterial genome.…”

Section: Introductionmentioning

confidence: 99%

Alternative substrate-bound conformation of bacterial solute-binding protein involved in the import of mammalian host glycosaminoglycans

Oiki

Kamochi

Mikami

et al. 2017

Sci Rep

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Glycosaminoglycans (GAGs), constituted by repeating uronate and amino sugar units, are major components of mammalian extracellular matrices. Some indigenous and pathogenic bacteria target GAGs for colonization to and/or infection of host mammalian cells. In Gram-negative pathogenic Streptobacillus moniliformis, the solute-binding protein (Smon0123)-dependent ATP-binding cassette (ABC) transporter incorporates unsaturated GAG disaccharides into the cytoplasm after depolymerization by polysaccharide lyase. Smon0123, composed of N and C domains, adopts either a substrate-free open or a substrate-bound closed form by approaching two domains at 47° in comparison with the open form. Here we show an alternative 39°-closed conformation of Smon0123 bound to unsaturated chondroitin disaccharide sulfated at the C-4 and C-6 positions of N-acetyl-d-galactosamine residue (CΔ4S6S). In CΔ4S6S-bound Smon0123, Arg204 and Lys210 around the two sulfate groups were located at different positions from those at other substrate-bound 47°-closed conformations. Therefore, the two sulfate groups in CΔ4S6S shifted substrate-binding residue arrangements, causing dynamic conformational change. Smon0123 showed less affinity with CΔ4S6S than with non-sulfated and monosulfated substrates. ATPase activity of the Smon0123-dependent ABC transporter in the presence of CΔ4S6S was lower than that in the presence of other unsaturated chondroitin disaccharides, suggesting that CΔ4S6S-bound Smon0123 was unpreferable for docking with the ABC transporter.

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Glycan‐metabolizing enzymes in microbe–host interactions: the Streptococcus pneumoniae paradigm

2018

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Streptococcus pneumoniae is a frequent colonizer of the upper airways; however, it is also an accomplished pathogen capable of causing life-threatening diseases. To colonize and cause invasive disease, this bacterium relies on a complex array of factors to mediate the host-bacterium interaction. The respiratory tract is rich in functionally important glycoconjugates that display a vast range of glycans, and, thus, a key component of the pneumococcus-host interaction involves an arsenal of bacterial carbohydrate-active enzymes to depolymerize these glycans and carbohydrate transporters to import the products. Through the destruction of host glycans, the glycan-specific metabolic machinery deployed by S. pneumoniae plays a variety of roles in the host-pathogen interaction. Here, we review the processing and metabolism of the major host-derived glycans, including N- and O-linked glycans, Lewis and blood group antigens, proteoglycans, and glycogen, as well as some dietary glycans. We discuss the role of these metabolic pathways in the S. pneumoniae-host interaction, speculate on the potential of key enzymes within these pathways as therapeutic targets, and relate S. pneumoniae as a model system to glycan processing in other microbial pathogens.

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Metabolic Fate of Unsaturated Glucuronic/Iduronic Acids from Glycosaminoglycans

Cited by 22 publications

References 50 publications

Probiotics in human gut microbiota can degrade host glycosaminoglycans

Probiotics in human gut microbiota can degrade host glycosaminoglycans

Alternative substrate-bound conformation of bacterial solute-binding protein involved in the import of mammalian host glycosaminoglycans

Glycan‐metabolizing enzymes in microbe–host interactions: the Streptococcus pneumoniae paradigm

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