D-Lyxose

The Dose-Response Effect of Fluoride Exposure on the Gut Microbiome and Its Functional Pathways in Rats.[Pubmed:37999254]

Metabolites. 2023 Nov 17;13(11):1159.

Metabolic activities within the gut microbiome are intimately linked to human health and disease, especially within the context of environmental exposure and its potential ramifications. Perturbations within this microbiome, termed "gut microbiome perturbations", have emerged as plausible intermediaries in the onset or exacerbation of diseases following environmental chemical exposures, with fluoride being a compound of particular concern. Despite the well-documented adverse impacts of excessive fluoride on various human physiological systems-ranging from skeletal to neurological-the nuanced dynamics between fluoride exposure, the gut microbiome, and the resulting dose-response relationship remains a scientific enigma. Leveraging the precision of 16S rRNA high-throughput sequencing, this study meticulously examines the ramifications of diverse fluoride concentrations on the gut microbiome's composition and functional capabilities within Wistar rats. Our findings indicate a profound shift in the intestinal microbial composition following fluoride exposure, marked by a dose-dependent modulation in the abundance of key genera, including Pelagibacterium, Bilophila, Turicibacter, and Roseburia. Moreover, discernible alterations were observed in critical functional and metabolic pathways of the microbiome, such as D-Lyxose ketol-isomerase and DNA polymerase III subunit gamma/tau, underscoring the broad-reaching implications of fluoride exposure. Intriguingly, correlation analyses elucidated strong associations between specific bacterial co-abundance groups (CAGs) and these shifted metabolic pathways. In essence, fluoride exposure not only perturbs the compositional equilibrium of the gut microbiota but also instigates profound shifts in its metabolic landscape. These intricate alterations may provide a mechanistic foundation for understanding fluoride's potential toxicological effects mediated via gut microbiome modulation.

Construction of a Diagnostic Model for Small Cell Lung Cancer Combining Metabolomics and Integrated Machine Learning.[Pubmed:37706531]

Oncologist. 2024 Mar 4;29(3):e392-e401.

BACKGROUND: To date, no study has systematically explored the potential role of serum metabolites and lipids in the diagnosis of small cell lung cancer (SCLC). Therefore, we aimed to conduct a case-cohort study that included 191 cases of SCLC, 91 patients with lung adenocarcinoma, 82 patients with squamous cell carcinoma, and 97 healthy controls. METHODS: Metabolomics and lipidomics were applied to analyze different metabolites and lipids in the serum of these patients. The SCLC diagnosis model (d-model) was constructed using an integrated machine learning technology and a training cohort (n = 323) and was validated in a testing cohort (n=138). RESULTS: Eight metabolites, including 1-mristoyl-sn-glycero-3-phosphocholine, 16b-hydroxyestradiol, 3-phosphoserine, cholesteryl sulfate, D-Lyxose, dioctyl phthalate, DL-lactate and Leu-Phe, were successfully selected to distinguish SCLC from controls. The d-model was constructed based on these 8 metabolites and showed improved diagnostic performance for SCLC, with the area under curve (AUC) of 0.933 in the training cohort and 0.922 in the testing cohort. Importantly, the d-model still had an excellent diagnostic performance after adjusting the stage and related clinical variables and, combined with the progastrin-releasing peptide (ProGRP), showed the best diagnostic performance with 0.975 of AUC for limited-stage patients. CONCLUSION: This study is the first to analyze the difference between metabolomics and lipidomics and to construct a d-model to detect SCLC using integrated machine learning. This study may be of great significance for the screening and early diagnosis of SCLC patients.

Glass transition phenomena and dielectric relaxations in supercooled d-lyxose aqueous solutions.[Pubmed:37572627]

Carbohydr Res. 2023 Oct;532:108917.

Differential scanning calorimeter and broadband dielectric spectroscopy in a broad range of temperatures (150-300 K) were employed to study the D-Lyxose aqueous mixture at different hydration levels. Two relaxation processes were observed in all investigated D-Lyxose aqueous mixtures. A relaxation process (process-I) usually known as the primary relaxation mode which is accountable for the collective motion of D-Lyxose aqueous solution, was observed above the glass transition temperature (T(g)). Below T(g), another process designated as process-II was found which is mainly related to the water molecule relaxation inside the D-Lyxose matrix. The average relaxation times as a function of temperature and dielectric strengths of both observed relaxation processes (I & II) were analyzed for all hydration levels in D-Lyxose. It was identified that the relaxation amplitude of process-II in the D-Lyxose aqueous mixture was increased drastically and their activation energies were found to be approximately independent of the content of water above critical concentration, x(c) = 0.28. This suggests that the dynamical process observed above x(c) was dominated by the presence of water clusters. In the current aqueous mixture, the critical content of water (x(c)) is slightly higher as compared to previously reported aqueous mixtures, indicating a more cooperative nature of water molecules with a D-Lyxose matrix. Additionally, the T(g) of pure water was estimated at 128 +/- 5.8 K from the extrapolation of DSC T(g) data of the D-Lyxose aqueous solution by using the well-known Gordon-Taylor equation. Our current result gives further support to the well-accepted glass transition (T(g)) of pure water.

Engineering the thermostability of d-lyxose isomerase from Caldanaerobius polysaccharolyticus via multiple computer-aided rational design for efficient synthesis of d-mannose.[Pubmed:37168606]

Synth Syst Biotechnol. 2023 Apr 21;8(2):323-330.

d-Mannose is an attractive functional sugar that exhibits many physiological benefits on human health. The demand for low-calorie sugars and sweeteners in foods are increasingly available on the market. Some sugar isomerases, such as D-Lyxose isomerase (d-LIase), can achieve an isomerization reaction between d-mannose and d-fructose. However, the weak thermostability of d-LIase limits its efficient conversion from d-fructose to d-mannose. Nonetheless, few studies are available that have investigated the molecular modification of d-LIase to improve its thermal stability. In this study, computer-aided tools including FireProt, PROSS, and Consensus Finder were employed to jointly design d-LIase mutants with improved thermostability for the first time. Finally, the obtained five-point mutant M5 (N21G/E78P/V58Y/C119Y/K170P) showed high thermal stability and catalytic activity. The half-life of M5 at 65 degrees C was 10.22 fold, and the catalytic efficiency towards 600 g/L of d-fructose was 2.6 times to that of the wild type enzyme, respectively. Molecular dynamics simulation and intramolecular forces analysis revealed a thermostability mechanism of highly rigidity conformation, newly formed hydrogen bonds and pi-cation interaction between and within protein domains, and redistributed surface electrostatic charges for the mutant M5. This research provided a promising d-LIase mutant for the industrial production of d-mannose from d-fructose.

A new synthesis of d-lyxose from d-arabinose.[Pubmed:37001234]

Carbohydr Res. 2023 Apr;526:108782.

A new synthesis of rare D-Lyxose from easily available d-arabinose is disclosed. The route includes 7 steps with a total 40% yield. Inversion of configuration at C3 promoted by DAST reagent is utilized on trans-2,3-di-hydroxy pentofuranose to provide cis-2,3-di-hydroxy pentofuranose, which is hardly synthesized using normal method.

Providencia manganoxydans sp. nov., a Mn(II)-oxidizing bacterium isolated from heavy metal contaminated soils in Hunan Province, China.[Pubmed:35930465]

Int J Syst Evol Microbiol. 2022 Aug;72(8).

A facultatively anaerobic, Gram-negative, rod-shaped bacterial strain designated as LLDRA6(T), was isolated from heavy metal contaminated soils collected near a ceased smelting factory at Zhuzhou, Hunan Province, China. Strain LLDRA6(T) has the ability to oxidize Mn(II) and generate biogenic manganese oxides. The strain can grow in a wide range of temperature from 10-42 degrees C and pH from 5 to 10. Comparative analysis of its complete 16S rRNA gene sequence suggests that strain LLDRA6(T) is highly similar to species within the genus Providencia. The complete genome of LLDRA6(T) is 4 342 370 bp with 40.18 mol% of G+C content and contains no plasmids. In comparison to the genomes of type strains in Providencia, LLDRA6(T) shows average nucleotide identity values between 76.60 and 80.89 %, and digital DNA-DNA hybridization values in a range of 21.2-24.6 %. Both multilocus sequence analysis and genomic phylogenetics indicate a new taxonomic status for LLDRA6(T) in Providencia. Chemotaxonomic analyses for LLDRA6(T) show that the predominant cellular fatty acids are C(16 : 0), C(14 : 0) and cyclo-C(17 : 0), accounting for 32.7, 16.1 and 10.3 % of total fatty acids, respectively. The polar lipids consist of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, four unidentified aminolipids, one unidentified phospholipid and three unidentified lipids. Within the cell wall, ribose and meso-diaminopimelic acid are the characteristic constituents for saccharides and amino acids, respectively. Respiratory quinones on cell membranes are composed of menaquinone (MK) and ubiquinone (coenzyme Q), including MK-8 (100.0 %), Q-7 (13.7 %) and Q-8 (86.3 %). Moreover, the positive results from D-Lyxose and d-mannitol fermentation tests indicate that LLDRA6(T) is totally different from all the type strains within the genus Providencia. In summary, strain LLDRA6(T) represents a novel species in the genus Providencia, for which the name Providencia manganoxydans sp. nov. (type strain LLDRA6(T)=CCTCC AB 2021154(T)=KCTC 92091(T)) is proposed.

Anoxybacillus karvacharensis sp. nov., a novel thermophilic bacterium isolated from the Karvachar geothermal spring in Nagorno-Karabakh.[Pubmed:34596507]

Int J Syst Evol Microbiol. 2021 Oct;71(10):005035.

Twelve thermophilic Anoxybacillus strains were isolated from sediment and water samples from a Karvachar hot spring located in the northern part of Nagorno-Karabakh. Based on phenotypic, chemotaxonomic and phylogenetic characteristics, one of the isolates, designated strain K1(T), was studied in detail. The cells are straight, motile rods that are 0.2-0.4x2.3-7.2 microm in size. The strain is a Gram-stain-positive, moderately thermophilic facultative anaerobe with an optimum growth temperature of 60-65 degrees C and a growth temperature range of 45-70 degrees C. Growth of strain K1(T) was observed at pH 6-11 (optimum, pH 8-9) and was inhibited in the presence of NaCl concentrations above 2.5 % (optimum, 1-1.5 %). The isolate could utilize a wide variety of carbon sources, including d-arabinose, d-ribose, d-galactose, d-fructose, d-mannitol, maltose, aesculin, melibiose, sucrose, trehalose, raffinose, amidone, glycogen, turanose, D-Lyxose, d-tagatose, potassium gluconate and 2-keto-gluconate. The strain was able to hydrolyse starch, casein and gelatin, was positive for oxidase and catalase, and reduced nitrate to nitrite, but was negative for H(2)S production. Production of urease and indole was not observed. The major cellular fatty acids were C(15 : 0) iso, C(16 : 0) and C(17 : 0) iso (52.5, 13.6 and 19.6 % of total fatty acids, respectively). Strain K1(T) shares >99 % 16S rRNA sequence similarity and a genomic average nucleotide identity value of 94.5 % with its closest relative, Anoxybacillus flavithermus DSM 2641(T), suggesting that it represents a separate and novel species, for which the name Anoxybacillus karvacharensis sp. nov. is proposed. The type strain of Anoxybacillus karvacharensis is K1(T) (=DSM 106524(T)=KCTC 15807(T)).

New Unnatural Gallotannins: A Way toward Green Antioxidants, Antimicrobials and Antibiofilm Agents.[Pubmed:34439536]

Antioxidants (Basel). 2021 Aug 13;10(8):1288.

Nature has been a source of inspiration for the development of new pharmaceutically active agents. A series of new unnatural gallotannins (GTs), derived from D-Lyxose, d-ribose, l-rhamnose, d-mannose, and d-fructose have been designed and synthesized in order to study the protective and antimicrobial effects of synthetic polyphenols that are structurally related to plant-derived products. The structures of the new compounds were confirmed by various spectroscopic methods. Apart from spectral analysis, the antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging and iron reducing power (FRAP) assays. Antibacterial activity of compounds was tested in vitro against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 (reference and control strains), three methicillin-resistant isolates of S. aureus, and three isolates of vancomycin-resistant E. faecalis. For screening of antimycobacterial effect, a virulent isolate of Mycobacterium tuberculosis and two non-tuberculous mycobacteria were used. Furthermore, antibiofilm activity of structurally different GTs against S. aureus, and their ability to inhibit sortase A, were inspected. Experimental data revealed that the studied GTs are excellent antioxidants and radical-scavenging agents. The compounds exhibited only a moderate antibacterial effect against Gram-positive pathogens S. aureus and E. faecalis and were practically inactive against mycobacteria. However, they were efficient inhibitors and disruptors of S. aureus biofilms in sub-MIC concentrations, and interacted with the quorum-sensing system in Chromobacteriumviolaceum. Overall, these findings suggest that synthetic GTs could be considered as promising candidates for pharmacological, biomedical, consumer products, and for food industry applications.

Biochemical and Structural Characterisation of a Novel D-Lyxose Isomerase From the Hyperthermophilic Archaeon Thermofilum sp.[Pubmed:34422783]

Front Bioeng Biotechnol. 2021 Aug 6;9:711487.

A novel D-Lyxose isomerase has been identified within the genome of a hyperthermophilic archaeon belonging to the Thermofilum species. The enzyme has been cloned and over-expressed in Escherichia coli and biochemically characterised. This enzyme differs from other enzymes of this class in that it is highly specific for the substrate D-Lyxose, showing less than 2% activity towards mannose and other substrates reported for lyxose isomerases. This is the most thermoactive and thermostable lyxose isomerase reported to date, showing activity above 95 degrees C and retaining 60% of its activity after 60 min incubation at 80 degrees C. This lyxose isomerase is stable in the presence of 50% (v/v) of solvents ethanol, methanol, acetonitrile and DMSO. The crystal structure of the enzyme has been resolved to 1.4-1.7 A. resolution in the ligand-free form and in complexes with both of the slowly reacting sugar substrates mannose and fructose. This thermophilic lyxose isomerase is stabilised by a disulfide bond between the two monomers of the dimeric enzyme and increased hydrophobicity at the dimer interface. These overall properties of high substrate specificity, thermostability and solvent tolerance make this lyxose isomerase enzyme a good candidate for potential industrial applications.

Green synthesis of 1,5-dideoxy-1,5-imino-ribitol and 1,5-dideoxy-1,5-imino-DL-arabinitol from natural D-sugars over Au/Al(2)O(3) and SO(4)(2-)/Al(2)O(3) catalysts.[Pubmed:34413372]

Sci Rep. 2021 Aug 19;11(1):16928.

A green synthetic route for the synthesis of some potential enzyme active hydroxypiperidine iminosugars including 1,5-dideoxy-1,5-imino-ribitol and 1,5-dideoxy-1,5-imino-DL-arabinitol, starting from commercially available D-ribose and D-Lyxose was tested out. Heterogeneous catalysts including Au/Al(2)O(3), SO(4)(2-)/Al(2)O(3) as well as environmentally friendly reagents were employed into several critical reaction of the route. The synthetic route resulted in good overall yields of 1,5-dideoxy-1,5-imino-ribitol of 54%, 1,5-dideoxy-1,5-imino-D-arabinitol of 48% and 1,5-dideoxy-1,5-imino-L-arabinitol of 46%. The Au/Al(2)O(3) catalyst can be easily recovered from the reaction mixture and reused with no loss of activity.

Mechanism of the Immunomodulatory Effect of the Combination of Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus on Immunocompromised Rats.[Pubmed:34211480]

Front Immunol. 2021 Jun 15;12:694344.

Immunodeficiency is a very common condition in suboptimal health status and during the development or treatment of many diseases. Recently, probiotics have become an important means for immune regulation. The present study aimed to investigate the mechanism of the immunomodulatory effect of a combination of live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus (CBLEB), which is a drug used by approximately 10 million patients every year, on cyclophosphamide-immunosuppressed rats. Cyclophosphamide (40 mg/kg) was intraperitoneally injected to induce immunosuppression in a rat model on days 1, 2, 3, and 10. Starting from day 4, the rats were continuously gavaged with CBLEB solution for 15 days. The samples were collected to determine routine blood test parameters, liver and kidney functions, serum cytokine levels, gut microbiota, fecal and serum metabolomes, transcriptomes, and histopathological features. The results indicated that CBLEB treatment reduced cyclophosphamide-induced death, weight loss, and damage to the gut, liver, spleen, and lungs and eliminated a cyclophosphamide-induced increase in the mean hemoglobin content and GGT, M-CSF, and MIP-3alpha levels and a decrease in the red blood cell distribution width and total protein and creatinine levels in the blood. Additionally, CBLEB corrected cyclophosphamide-induced dysbiosis of the gut microbiota and eliminated all cyclophosphamide-induced alterations at the phylum level in rat feces, including the enrichment in Proteobacteria, Fusobacteriota, and Actinobacteriota and depletion of Spirochaetota and Cyanobacteria. Furthermore, CBLEB treatment alleviated cyclophosphamide-induced alterations in the whole fecal metabolome profile, including enrichment in 1-heptadecanol, succinic acid, hexadecane-1,2-diol, nonadecanoic acid, and pentadecanoic acid and depletion of benzenepropanoic acid and hexane. CBLEB treatment also alleviated cyclophosphamide-induced enrichment in serum D-Lyxose and depletion of serum succinic acid, D-galactose, L-5-oxoproline, L-alanine, and malic acid. The results of transcriptome analysis indicated that the mechanism of the effect of CBLEB was related to the induction of recovery of cyclophosphamide-altered carbohydrate metabolism and signal transduction. In conclusion, the present study provides an experimental basis and comprehensive analysis of application of CBLEB for the treatment of immunodeficiency.

Evaluation of surface active and antimicrobial properties of alkyl D-lyxosides and alkyl L-rhamnosides as green surfactants.[Pubmed:33736217]

Chemosphere. 2021 May;271:129818.

The use of carbohydrates, as a part of surface-active compounds, has been studied due to their biodegradability and nontoxic profile. A series of alkyl glycosides containing D-Lyxose and l-rhamnose with alkyl chains of 8-12 carbon atoms were investigated. The effects of structural variations on their physico-chemical and biological properties have been evaluated for a detailed understanding of their properties. Alkyl glycosides were tested on their toxicity against bacterial cells of the genus Pseudomonas (MTT assay), microbiological adhesion to hydrocarbons (MATH assay), cell surface hydrophobicity (Congo red assay), cell membrane permeability (crystal violet assay), and bacterial biofilm formation. Furthermore, their antifungal activity against two pathogenic microorganisms Candida albicans and Aspergillus niger was investigated using the disc diffusion method. Toxicological studies revealed that compounds could reduce the metabolic activity of bacterial cells only moderately but they increased the hydrophobicity of cell surface in Pseudomonas strains. In addition, alkyl glycosides changed the permeability of the cell membranes to the level of 30-40% for this strain. The compounds with an even number of carbon atoms in their alkyl chain promoted stronger bacterial biofilm formation on the glass surface. All studied derivatives demonstrated very strong antifungal activity against fungus A. niger but very small effect against C. albicans. Overall, the results showed that long-chain alkyl glycosides could be considered as inexpensive, biocompatible, nontoxic agents, and serve for the surface design to avoid bacterial adhesion as an alternative solution to antibiotic treatment.

Identification of a novel recombinant D-lyxose isomerase from Thermoprotei archaeon with high thermostable, weak-acid and nickel ion dependent properties.[Pubmed:32750472]

Int J Biol Macromol. 2020 Dec 1;164:1267-1274.

Recently, production of D-mannose becomes a hotspot owing to it exhibiting many physiological functions on people's health and wide applications in food and pharmaceutical field. The use of biological enzymes to production of D-mannose is of particular receiving considerable concerns due to it possessing many merits over chemical synthesis and plant extraction strategies. D-Lyxose isomerase (D-LIase) plays a pivotal role in preparation of D-mannose from d-fructose through isomerization reaction. Thus, a novel putative D-LIase from thermophiles strain Thermoprotei archaeon which was expressed in E. coli BL21(DE3) was first identified and biochemically characterized. The recombinant D-LIase showed an optimal temperature of 80 and 85 degrees C and pH of 6.5. It was highly thermostable at 70 degrees C and 80 degrees C after incubating for 48 h and 33 h, respectively, with retaining over 50% of the initial activity. A lower concentration of Ni(2+) (0.5 mM) could greatly increase the activity by 25-fold, which was rare reported in other D-LIases. It was a dimer structure with melting temperature of 88.3 degrees C. Under the optimal conditions, 15.8 g L(-1) of D-mannose and 33.8 g L(-1) of D-xylulose were produced from 80 g L(-1) of d-fructose and D-Lyxose, respectively. This work provided a promising candidate sugar isomerase T. archaeon D-LIase for the production of D-mannose and D-xylulose.

Characterization of a recombinant D-mannose-producing D-lyxose isomerase from Caldanaerobius polysaccharolyticus.[Pubmed:32527523]

Enzyme Microb Technol. 2020 Aug;138:109553.

Recently, functional sugars, such as d-mannose, have attracted considerable attention due to their excellent physiological benefits for human health and wide applications in food and pharmaceutical industries. Therefore, d-mannose production using a sugar isomerase such as D-Lyxose isomerase (d-LIase) has emerged as a research hotspot owing to its advantages over plant extraction and chemical synthesis methods. In this study, a putative d-LIase gene from Caldanaerobius polysaccharolyticus was cloned and expressed in Escherichia coli. Then, a biochemical characterization of the recombinant d-LIase was carried out and its potential use in d-mannose production also assessed. Results showed that d-LIase exhibited its maximum activity under these optimal conditions: temperature of 65 degrees C, a pH of 6.5, and the Mn(2+) metal ion. The d-LIase was active at pH 6.0-8.0; it was also quite thermostable up to 60 degrees C and approximately 85 % of its maximum activity was retained after incubating for 4 h. Further, our Nano-DSC analysis determined that its melting temperature (T(m)) was 70.74 degrees C. Using 100, 300, and 500 g L(-1) of d-fructose as substrate, 25.6, 74.4, and 115 g L(-1) of d-mannose were produced respectively, corresponding to a conversion rate of 25.6 %, 24.8 %, and 23.0 % under optimal conditions. Taken together, our results provide evidence for a promising candidate d-LIase for producing d-mannose directly from d-fructose.

Production of l-ribose from l-arabinose by co-expression of l-arabinose isomerase and d-lyxose isomerase in Escherichia coli.[Pubmed:31731969]

Enzyme Microb Technol. 2020 Jan;132:109443.

l-Ribose is an important pharmaceutical intermediate that is used in the synthesis of numerous antiviral and anticancer drugs. However, it is a non-natural and expensive rare sugar. Recently, the enzymatic synthesis of l-ribose has attracted considerable attention owing to its considerable advantages over chemical approaches. In this work, a new strategy was developed for the production of l-ribose from the inexpensive starting material l-arabinose. The l-arabinose isomerase (l-AIase) gene from Alicyclobacillus hesperidum and the D-Lyxose isomerase (d-LIase) gene from Thermoflavimicrobium dichotomicum were cloned and co-expressed in Escherichia coli, resulting in recombinant cells harboring the vector pCDFDuet-Alhe-LAI/Thdi-DLI. The co-expression system exhibited optimal activity at a temperature of 70  degrees C and pH 6.0, and the addition of Co(2+) enhanced the catalytic activity by 27.8-fold. The system containing 50 g L(-1) of recombinant cells were relatively stable up to 55  degrees C. The co-expression system (50 g L(-1) of recombinant cells) afforded 20.9, 39.7, and 50.3 g L(-1) of l-ribose from initial l-arabinose concentrations of 100, 300, and 500 g L(-1), corresponding to conversion rate of 20.9%, 13.2%, and 10.0%, respectively. Overall, this study provides a viable approach for producing l-ribose from l-arabinose under slightly acidic conditions using a co-expression system harboring l-AIase and d-LIase genes.