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Molecules (Basel, Switzerland) Aug 2022Rhamnose-associated molecules are attracting attention because they are present in bacteria but not mammals, making them potentially useful as antibacterial agents.... (Review)
Review
Rhamnose-associated molecules are attracting attention because they are present in bacteria but not mammals, making them potentially useful as antibacterial agents. Additionally, they are also valuable for tumor immunotherapy. Thus, studies on the functions and biosynthetic pathways of rhamnose-containing compounds are in progress. In this paper, studies on the biosynthetic pathways of three rhamnose donors, i.e., deoxythymidinediphosphate-L-rhamnose (dTDP-Rha), uridine diphosphate-rhamnose (UDP-Rha), and guanosine diphosphate rhamnose (GDP-Rha), are firstly reviewed, together with the functions and crystal structures of those associated enzymes. Among them, dTDP-Rha is the most common rhamnose donor, and four enzymes, including glucose-1-phosphate thymidylyltransferase RmlA, dTDP-Glc-4,6-dehydratase RmlB, dTDP-4-keto-6-deoxy-Glc-3,5-epimerase RmlC, and dTDP-4-keto-Rha reductase RmlD, are involved in its biosynthesis. Secondly, several known rhamnosyltransferases from , , , , and are discussed. In these studies, however, the functions of rhamnosyltransferases were verified by employing gene knockout and radiolabeled substrates, which were almost impossible to obtain and characterize the products of enzymatic reactions. Finally, the application of rhamnose-containing compounds in disease treatments is briefly described.
Topics: Biosynthetic Pathways; Racemases and Epimerases; Rhamnose; Thymine Nucleotides; Uridine Diphosphate
PubMed: 36014553
DOI: 10.3390/molecules27165315 -
Molecules (Basel, Switzerland) Feb 2023Aging is a complex physiological process that can be accelerated by chemical (high blood glucose levels) or physical (solar exposure) factors. It is accompanied by the...
Aging is a complex physiological process that can be accelerated by chemical (high blood glucose levels) or physical (solar exposure) factors. It is accompanied by the accumulation of altered molecules in the human body. The accumulation of oxidatively modified and glycated proteins is associated with inflammation and the progression of chronic diseases (aging). The use of antiglycating agents is one of the recent approaches in the preventive strategy of aging and natural compounds seem to be promising candidates. Our study focused on the anti-aging effect of the flavonoid hesperetin, its glycoside hesperidin and its carbohydrate moieties rutinose and rhamnose on young and physiologically aged normal human dermal fibroblasts (NHDFs). The anti-aging activity of the test compounds was evaluated by measuring matrix metalloproteinases (MMPs) and inflammatory interleukins by ELISA. The modulation of elastase, hyaluronidase, and collagenase activity by the tested substances was evaluated spectrophotometrically by tube tests. Rutinose and rhamnose inhibited the activity of pure elastase, hyaluronidase, and collagenase. Hesperidin and hesperetin inhibited elastase and hyaluronidase activity. In skin aging models, MMP-1 and MMP-2 levels were reduced after application of all tested substances. Collagen I production was increased after the application of rhamnose and rutinose.
Topics: Humans; Collagenases; Hesperidin; Hyaluronoglucosaminidase; Pancreatic Elastase; Rhamnose; Skin Aging
PubMed: 36838716
DOI: 10.3390/molecules28041728 -
Molecular Microbiology Apr 2019The halophilic archaeon Haloferax volcanii utilizes l-rhamnose as a sole carbon and energy source. It is shown that l-rhamnose is taken up by an ABC transporter and is...
The halophilic archaeon Haloferax volcanii utilizes l-rhamnose as a sole carbon and energy source. It is shown that l-rhamnose is taken up by an ABC transporter and is oxidatively degraded to pyruvate and l-lactate via the diketo-hydrolase pathway. The genes involved in l-rhamnose uptake and degradation form a l-rhamnose catabolism (rhc) gene cluster. The rhc cluster also contains a gene, rhcR, that encodes the transcriptional regulator RhcR which was characterized as an activator of all rhc genes. 2-keto-3-deoxy-l-rhamnonate, a metabolic intermediate of l-rhamnose degradation, was identified as inducer molecule of RhcR. The essential function of rhc genes for uptake and degradation of l-rhamnose was proven by the respective knockout mutants. Enzymes of the diketo-hydrolase pathway, including l-rhamnose dehydrogenase, l-rhamnonolactonase, l-rhamnonate dehydratase, 2-keto-3-deoxy-l-rhamnonate dehydrogenase and 2,4-diketo-3-deoxy-l-rhamnonate hydrolase, were characterized. Further, genes of the diketo-hydrolase pathway were also identified in the hyperthermophilic crenarchaeota Vulcanisaeta distributa and Sulfolobus solfataricus and selected enzymes were characterized, indicating the presence of the diketo-hydrolase pathway in these archaea. Together, this is the first comprehensive description of l-rhamnose catabolism in the domain of archaea.
Topics: ATP-Binding Cassette Transporters; Carbohydrate Dehydrogenases; Carbohydrate Metabolism; Genes, Archaeal; Haloferax volcanii; Multigene Family; Oxidoreductases; Rhamnose; Sulfolobus solfataricus
PubMed: 30707467
DOI: 10.1111/mmi.14213 -
International Journal of Molecular... Sep 2022Biosurfactants are naturally occurring amphiphiles that are being actively pursued as alternatives to synthetic surfactants in cleaning, personal care, and cosmetic...
Biosurfactants are naturally occurring amphiphiles that are being actively pursued as alternatives to synthetic surfactants in cleaning, personal care, and cosmetic products. On the basis of their ability to mobilize and disperse hydrocarbons, biosurfactants are also involved in the bioremediation of oil spills. Rhamnolipids are low molecular weight glycolipid biosurfactants that consist of a mono- or di-rhamnose head group and a hydrocarbon fatty acid chain. We examine here the micellization of purified mono-rhamnolipids and di-rhamnolipids in aqueous solutions and their adsorption on model solid surfaces. Rhamnolipid micellization in water is endothermic; the CMC (critical micellization concentration) of di-rhamnolipid is lower than that of mono-rhamnolipid, and both CMCs decrease upon NaCl addition. Rhamnolipid adsorption on gold surface is mostly reversible and the adsorbed layer is rigid. A better understanding of biosurfactant self-assembly and adsorption properties is important for their utilization in consumer products and environmental applications.
Topics: Adsorption; Fatty Acids; Glycolipids; Gold; Hydrocarbons; Rhamnose; Sodium Chloride; Surface-Active Agents; Water
PubMed: 36232408
DOI: 10.3390/ijms231911090 -
The Journal of Biological Chemistry Oct 2022Rhamnose-rich cell wall polysaccharides (Rha-CWPSs) have emerged as crucial cell wall components of numerous Gram-positive, ovoid-shaped bacteria-including streptococci,... (Review)
Review
Rhamnose-rich cell wall polysaccharides (Rha-CWPSs) have emerged as crucial cell wall components of numerous Gram-positive, ovoid-shaped bacteria-including streptococci, enterococci, and lactococci-of which many are of clinical or biotechnological importance. Rha-CWPS are composed of a conserved polyrhamnose backbone with side-chain substituents of variable size and structure. Because these substituents contain phosphate groups, Rha-CWPS can also be classified as polyanionic glycopolymers, similar to wall teichoic acids, of which they appear to be functional homologs. Recent advances have highlighted the critical role of these side-chain substituents in bacterial cell growth and division, as well as in specific interactions between bacteria and infecting bacteriophages or eukaryotic hosts. Here, we review the current state of knowledge on the structure and biosynthesis of Rha-CWPS in several ovoid-shaped bacterial species. We emphasize the role played by multicomponent transmembrane glycosylation systems in the addition of side-chain substituents of various sizes as extracytoplasmic modifications of the polyrhamnose backbone. We provide an overview of the contribution of Rha-CWPS to cell wall architecture and biogenesis and discuss current hypotheses regarding their importance in the cell division process. Finally, we sum up the critical roles that Rha-CWPS can play as bacteriophage receptors or in escaping host defenses, roles that are mediated mainly through their side-chain substituents. From an applied perspective, increased knowledge of Rha-CWPS can lead to advancements in strategies for preventing phage infection of lactococci and streptococci in food fermentation and for combating pathogenic streptococci and enterococci.
Topics: Bacteriophages; Cell Wall; Gram-Positive Bacteria; Polysaccharides; Rhamnose; Teichoic Acids; Cell Division
PubMed: 36113580
DOI: 10.1016/j.jbc.2022.102488 -
Scientific Reports Jun 2016The rhamnose utilization pathway in Pichia pastoris has not been clarified although this strain can grow well on rhamnose as a sole carbon source. In this study, four...
The rhamnose utilization pathway in Pichia pastoris has not been clarified although this strain can grow well on rhamnose as a sole carbon source. In this study, four genes, PAS_chr4_0338, PAS_chr4_0339, PAS_chr4_0340, and PAS_chr4_0341, were, for the first time, predicted to be involved in rhamnose metabolism along with the previously identified gene PAS_chr1_4-0075. Moreover, expression of these genes, especially PAS_chr4_0341 and PAS_chr1_4-0075 designated as LRA4 and LRA3, was confirmed to significantly increase and clearly decrease in the presences of rhamnose and glucose, respectively. LRA4 encoding a putative L-2-keto-3-deoxyrhamnonate aldolase, was further confirmed via gene disruption and gene complementation to participate in rhamnose metabolism. Using β-galactosidase and green fluorescent protein as reporters, the promoters of LRA4 and LRA3 performed well in driving efficient production of heterologous proteins. By using food grade rhamnose instead of the toxic compound methanol as the inducer, the two promoters would be excellent candidates for driving the production of food-grade and therapeutically important recombinant proteins.
Topics: Artificial Gene Fusion; Biotechnology; Gene Expression Profiling; Gene Knockout Techniques; Genes, Fungal; Genes, Reporter; Genetic Complementation Test; Glucose; Green Fluorescent Proteins; Metabolic Networks and Pathways; Pichia; Promoter Regions, Genetic; Rhamnose; Technology, Pharmaceutical; beta-Galactosidase
PubMed: 27256707
DOI: 10.1038/srep27352 -
Molecules (Basel, Switzerland) Apr 2023The use of radiolabeled glucose for PET imaging resulted in the most commonly used tracer in the clinic, 2-deoxy-2-[F]fluoroglucose (FDG). More recently, other...
The use of radiolabeled glucose for PET imaging resulted in the most commonly used tracer in the clinic, 2-deoxy-2-[F]fluoroglucose (FDG). More recently, other radiolabeled sugars have been reported for various applications, including imaging tumors and infections. Therefore, in this study, we developed a series of fluorine-18-labeled L-rhamnose derivatives as potential PET tracers of various fungal and bacterial strains. Acetyl-protected triflate precursors of rhamnose were prepared and radiolabeled with fluorine-18 followed by hydrolysis to produce L-deoxy [F]fluororhamnose. The overall radiochemical yield was 7-27% in a 90 min synthesis time with a radiochemical purity of 95%. In vivo biodistribution of the ligands using PET imaging showed that 2-deoxy-2-[F]fluoro-L-rhamnose is stable for at least up to 60 min in mice and eliminated via renal clearance. The tracer also exhibited minimal tissue or skeletal uptake in healthy mice resulting in a low background signal.
Topics: Mice; Animals; Rhamnose; Tissue Distribution; Cell Line, Tumor; Fluorine Radioisotopes; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 37175182
DOI: 10.3390/molecules28093773 -
International Journal of Molecular... Feb 2022Rhamnolipids are becoming an important class of glycolipid biosurfactants. Herein, we describe for the first time the enzymatic synthesis of rhamnose fatty acid esters...
Rhamnolipids are becoming an important class of glycolipid biosurfactants. Herein, we describe for the first time the enzymatic synthesis of rhamnose fatty acid esters by the transesterification of rhamnose with fatty acid vinyl esters, using lipase from as a biocatalyst. The use of this lipase allows excellent catalytic activity in the synthesis of 4--acylrhamnose (99% conversion and full regioselectivity) after 3 h of reaction using tetrahydrofuran (THF) as the reaction media and an excess of vinyl laurate as the acyl donor. The role of reaction conditions, such as temperature, the substrates molar ratio, organic reaction medium and acyl donor chain-length, was studied. Optimum conditions were found using 35 °C, a molar ratio of 1:3 (rhamnose:acyldonor), solvents with a low logP value, and fatty acids with chain lengths from C4 to C18 as acyl donors. In hydrophilic solvents such as THF and acetone, conversions of up to 99-92% were achieved after 3 h of reaction. In a more sustainable solvent such as 2-methyl-THF (2-MeTHF), high conversions were also obtained (86%). Short and medium chain acyl donors (C4-C10) allowed maximum conversions after 3 h, and long chain acyl donors (C12-C18) required longer reactions (5 h) to get 99% conversions. Furthermore, scaled up reactions are feasible without losing catalytic action and regioselectivity. In order to explain enzyme regioselectivity and its ability to accommodate ester chains of different lengths, homology modelling, docking studies and molecular dynamic simulations were performed to explain the behaviour observed.
Topics: Biocatalysis; Enzymes, Immobilized; Esterification; Esters; Fatty Acids; Hydrophobic and Hydrophilic Interactions; Laurates; Lipase; Pseudomonas stutzeri; Rhamnose; Solvents; Vinyl Compounds
PubMed: 35216354
DOI: 10.3390/ijms23042239 -
International Journal of Molecular... Nov 2022is the causative agent of one of the most widespread sexually transmitted diseases in the world. The adhesion of the parasite to the vaginal epithelial cells is...
is the causative agent of one of the most widespread sexually transmitted diseases in the world. The adhesion of the parasite to the vaginal epithelial cells is mediated by specific proteins and by a complex glycan structure, the lipoglycan (TvLG), which covers the pathogen surface. L-rhamnose is an important component of TvLG, comprising up to 40% of the monosaccharides. Thus, the inhibition of its production could lead to a severe alteration in the TvLG structure, making the L-rhamnose biosynthetic pathway an attractive pharmacologic target. We report the identification and characterization of the first committed and limiting step of the L-rhamnose biosynthetic pathway, UDP-D-glucose 4,6-dehydratase (UGD, EC 4.2.1.76). The enzyme shows a strong preference for UDP-D-glucose compared to dTDP-D-glucose; we propose that the mechanism underlying the higher affinity for the UDP-bound substrate is mediated by the differential recognition of ribose versus the deoxyribose of the nucleotide moiety. The identification of the enzymes responsible for the following steps of the L-rhamnose pathway (epimerization and reduction) was more elusive. However, sequence analyses suggest that in L-rhamnose synthesis proceeds through a mechanism different from the typical eukaryotic pathways, displaying intermediate features between the eukaryotic and prokaryotic pathways and involving separate enzymes for the epimerase and reductase activities, as observed in bacteria. Altogether, these results form the basis for a better understanding of the formation of the complex glycan structures on TvLG and the possible use of L-rhamnose biosynthetic enzymes for the development of selective inhibitors.
Topics: Female; Humans; Rhamnose; Biosynthetic Pathways; Glucose; Trichomonas vaginalis; Hydro-Lyases; Uridine Diphosphate
PubMed: 36498914
DOI: 10.3390/ijms232314587 -
Biotechnology Advances Dec 2023The Streptococcus genus comprises both commensal and pathogenic species. Additionally, Streptococcus thermophilus is exploited in fermented foods and in probiotic... (Review)
Review
The Streptococcus genus comprises both commensal and pathogenic species. Additionally, Streptococcus thermophilus is exploited in fermented foods and in probiotic preparations. The ecological and metabolic diversity of members of this genus is matched by the complex range of cell wall polysaccharides that they present on their cell surfaces. These glycopolymers facilitate their interactions and environmental adaptation. Here, current knowledge on the genetic and compositional diversity of streptococcal cell wall polysaccharides including rhamnose-glucose polysaccharides, exopolysaccharides and teichoic acids is discussed. Furthermore, the species-specific cell wall polysaccharide combinations and specifically highlighting the presence of rhamnose-glucose polysaccharides in certain species, which are replaced by teichoic acids in other species. This review highlights model pathogenic and non-pathogenic species for which there is considerable information regarding cell wall polysaccharide composition, structure and genetic information. These serve as foundations to predict and focus research efforts in other streptococcal species for which such data currently does not exist.
Topics: Teichoic Acids; Rhamnose; Polysaccharides; Streptococcus; Polysaccharides, Bacterial; Cell Wall; Glucose
PubMed: 37913948
DOI: 10.1016/j.biotechadv.2023.108279