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Biochemistry Nov 2010Everninomicin is a highly modified octasaccharide that belongs to the orthosomycin family of antibiotics and possesses potent Gram-positive antibiotic activity,...
Everninomicin is a highly modified octasaccharide that belongs to the orthosomycin family of antibiotics and possesses potent Gram-positive antibiotic activity, including broad-spectrum efficacy against multidrug resistant enterococci and Staphylococcus aureus. Among its distinctive structural features is a nitro sugar, l-evernitrose, analogues of which decorate a variety of natural products. Recently, we identified a nitrososynthase enzyme encoded by orf36 from Micromonospora carbonacea var. africana that mediates the flavin-dependent double oxidation of synthetically generated thymidine diphosphate (TDP)-l-epi-vancosamine to the corresponding nitroso sugar. Herein, we utilize a five-enzyme in vitro pathway both to verify that ORF36 catalyzes oxidation of biogenic TDP-l-epi-vancosamine and to determine whether ORF36 exhibits catalytic competence for any of its biosynthetic progenitors, which are candidate substrates for nitrososynthases in vivo. Progenitors solely undergo single-oxidation reactions and terminate in the hydroxylamine oxidation state. Performing the in vitro reactions in the presence of (18)O(2) establishes that molecular oxygen, rather than oxygen from water, is incorporated into ORF36-generated intermediates and products and identifies an off-pathway product that correlates with the oxidation product of a progenitor substrate. The 3.15 Å resolution X-ray crystal structure of ORF36 reveals a tetrameric enzyme that shares a fold with acyl-CoA dehydrogenases and class D flavin-containing monooxygenases, including the nitrososynthase KijD3. However, ORF36 and KijD3 have unusually open active sites in comparison to these related enzymes. Taken together, these studies map substrate determinants and allow the proposal of a minimal monooxygenase mechanism for amino sugar oxidation by ORF36.
Topics: Amino Sugars; Aminoglycosides; Anti-Bacterial Agents; Crystallography, X-Ray; Metabolic Networks and Pathways; Micromonospora; Mixed Function Oxygenases; Oxidation-Reduction
PubMed: 20866105
DOI: 10.1021/bi101336u -
Frontiers in Cellular and Infection... 2022The theory of "entero-pulmonary axis" proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the...
BACKGROUNDS AND PURPOSE
The theory of "entero-pulmonary axis" proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the potential mechanism of fecal microbiota transplantation (FMT) in the treatment of pneumonia, in order to provide new insights into the treatment of pneumonia.
METHODS
and C57/BL6 mice were used to construct the acute pneumonia mouse model, and FMT was treated. Histopathological changes in lung and spleen were observed by HE staining. The expression of CD25, Foxp3 and IL-17 was observed by immunofluorescence. The proportion of Treg and Th17 cells was analyzed by flow cytometry. Serum IL-6, LPS, and IFN-γ levels were detected by ELISA. The expression of TNF-α, IFN-γ, IL-6, IL-2, Foxp3, IL-17, IL-10, and TGFβ1 in lung tissue homogenate was detected by qRT-PCR. 16S rRNA sequencing and non-targeted metabolomics were used to analyze gut microbiota and metabolism.
RESULTS
caused the decrease of body weight, food and water intake, lung tissue, and spleen injury in mice with pneumonia. Meanwhile, it caused lung tissue and serum inflammation, and Treg/Th17 cell imbalance in mice with pneumonia. reduced the diversity and number of gut microbiota in pneumonia mice, resulting in metabolic disorders, superpathway of quinolone and alkylquinolone biosynthesis. It also led to the decrease of 2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis, and the enrichment of Amino sugar and nucleotide sugar metabolism. FMT with or without antibiotic intervention restored gut microbiota abundance and diversity, suppressed inflammation and tissue damage, and promoted an immunological balance of Treg/Th17 cells in mice with pneumonia. In addition, FMT inhibited the aerobactin biosynthesis, 4-hydroxyphenylacetate degradation, superpathway of lipopolysaccharide biosynthesis and L-arabinose degradation IV function of microbiota, and improved amino sugar and nucleotide sugar metabolism.
CONCLUSIONS
FMT restored the Treg/Th17 cells' balance and improved inflammation and lung injury in mice with pneumonia by regulating gut microbiota disturbance and metabolic disorder.
Topics: Amino Sugars; Animals; Forkhead Transcription Factors; Gastrointestinal Microbiome; Inflammation; Interleukin-17; Interleukin-6; Mice; Nucleotides; Pneumonia; Pseudomonas aeruginosa; Quinolones; RNA, Ribosomal, 16S; T-Lymphocytes, Regulatory; Th17 Cells
PubMed: 35782123
DOI: 10.3389/fcimb.2022.856633 -
Journal of Bacteriology Aug 1993The intracellular concentration of the enzyme glucosamine-6-phosphate synthase, encoded by the gene glmS in Escherichia coli, is repressed about threefold by growth on...
The intracellular concentration of the enzyme glucosamine-6-phosphate synthase, encoded by the gene glmS in Escherichia coli, is repressed about threefold by growth on the amino sugars glucosamine and N-acetylglucosamine. This regulation occurs at the level of glmS transcription. It is not due just to the presence of intracellular amino sugar phosphates, because mutations which derepress the genes of the nag regulon (coding for proteins involved in the uptake and metabolism of N-acetylglucosamine) also repress the expression of glmS in the absence of exogenous amino sugars.
Topics: Acetylglucosamine; Aldose-Ketose Isomerases; Amidohydrolases; Amino Sugars; Base Sequence; Carbohydrate Epimerases; Enzyme Induction; Enzyme Repression; Escherichia coli; Gene Expression Regulation, Bacterial; Glucosamine; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); Molecular Sequence Data; RNA, Messenger; Transcription, Genetic
PubMed: 8349539
DOI: 10.1128/jb.175.16.4951-4956.1993 -
Applied and Environmental Microbiology Jun 2016The antibiotic streptothricin (ST) possesses an amino sugar bound to an l-β-lysine (β-Lys) residue via a peptide bond. The peptide bond formation has been shown to be...
UNLABELLED
The antibiotic streptothricin (ST) possesses an amino sugar bound to an l-β-lysine (β-Lys) residue via a peptide bond. The peptide bond formation has been shown to be catalyzed by a nonribosomal peptide synthetase (NRPS) during ST biosynthesis. The focus of this study is the closely related ST analogue BD-12, which carries a glycine-derived side chain rather than a β-Lys residue. Here, in Streptomyces luteocolor NBRC13826, we describe our biosynthetic studies of BD-12, which revealed that the peptide bond between the amino sugar and the glycine residue is catalyzed by a Fem-like enzyme (Orf11) in a tRNA-dependent manner rather than by an NRPS. Although there have been several reports of peptide bond-forming tRNA-dependent enzymes, to our knowledge, Orf11 is the first enzyme that can accept an amino sugar as a substrate. Our findings clearly demonstrate that the structural diversity of the side chains of ST-type compounds in nature is generated in an unusual manner via two distinct peptide bond-forming mechanisms. Moreover, the identification and functional analysis of Orf11 resulted in not only the production of new ST-related compounds, but also the provision of new insights into the structure-activity relationship of the ST-related antibiotics.
IMPORTANCE
The antibiotic streptothricin (ST) possesses an amino sugar bound to an l-β-lysine (β-Lys) side chain via a peptide bond formed by a nonribosomal peptide synthetase (NRPS). BD-12, an analogue of ST, carries a glycine-derived side chain rather than β-Lys, and here, we describe the BD-12-biosynthetic gene cluster from Streptomyces luteocolor NBRC13826, which contains the orf11 gene encoding a novel tRNA-dependent peptide bond-forming enzyme. The unique Fem-like enzyme (Orf11) accepts the amino sugar as a substrate and mediates the peptide formation between the amino sugar intermediate and glycine. Our studies demonstrate that the structural diversity of the side chains of ST-related compounds in nature is generated via two distinct peptide bond-forming mechanisms.
Topics: Amino Sugars; Aminoacylation; Anti-Bacterial Agents; Metabolic Networks and Pathways; RNA, Transfer; Streptomyces; Streptothricins
PubMed: 27084005
DOI: 10.1128/AEM.00725-16 -
BMC Plant Biology Sep 2022Camellia oleifera Abel. (C. oleifera) is an important traditional woody species in China that produces edible oil. However, the current literature lacks a proper...
BACKGROUND
Camellia oleifera Abel. (C. oleifera) is an important traditional woody species in China that produces edible oil. However, the current literature lacks a proper understanding of C. oleifera's ability to adapt to different photoperiods.
RESULTS
Our results indicate that the photoperiod can significantly impact flowering time in C. oleifera. We grew a total of nine samples under the short day condition (SD), middle day condition (MD) and long day condition (LD). Transcriptome analysis yielded 66.94 Gb of high-quality clean reads, with an average of over 6.73 Gb of reads for per sample. Following assembly, a total of 120,080 transcripts were obtained and 94,979 unigenes annotated. A total of 3475 differentially expressed genes (DEGs) were identified between the SD_MD, SD_LD, and MD_LD gene sets. Moreover, WGCNA identified ten gene modules. Genes in pink module (92 genes) were positively correlated with SD, and negatively correlated with both MD and LD. Genes in the magenta module (42 genes) were positively correlated with MD and negatively correlated with both LD and SD. Finally, genes in the yellow module (1758 genes) were positively correlated with both SD and MD, but negatively correlated with LD. KEGG enrichment analysis revealed that genes in the pink, magenta, and yellow modules were involved in flavonoid biosynthesis, amino sugar and nucleotide sugar metabolism and circadian rhythm pathways. Additionally, eight hub genes (GI, AP2, WRKY65, SCR, SHR, PHR1, ERF106, and SCL3) were obtained through network analysis. The hub genes had high connectivity with other photoperiod-sensitive DEGs. The expression levels of hub genes were verified by qRT-PCR analysis.
CONCLUSION
An increase in light duration promotes earlier flowering of C. oleifera. Flavonoid biosynthesis, amino sugar and nucleotide sugar metabolism, and circadian rhythm pathways may function in the photoperiodic flowering pathway of C. oleifera. We also identified eight hub genes that may play a role in this pathway. Ultimately, this work contributes to our understanding of the photoperiodic flowering pathway of C. oleifera and further informs molecular breeding programs on the plant's photoperiodic sensitivity.
Topics: Amino Sugars; Camellia; Flavonoids; Nucleotides; Photoperiod; Rosaniline Dyes; Transcriptome
PubMed: 36089577
DOI: 10.1186/s12870-022-03798-0 -
Scientific Reports Nov 2016Infestation by the biotrophic pathogen Gymnosporangium asiaticum can be devastating for plant of the family Rosaceae. However, the phytopathology of this process has not...
Infestation by the biotrophic pathogen Gymnosporangium asiaticum can be devastating for plant of the family Rosaceae. However, the phytopathology of this process has not been thoroughly elucidated. Using a metabolomics approach, we discovered the intrinsic activities that induce disease symptoms after fungal invasion in terms of microbe-induced metabolic responses. Through metabolic pathway enrichment and mapping, we found that the host altered its metabolite levels, resulting in accumulation of tetrose and pentose sugar alcohols, in response to this fungus. We then used a multiple linear regression model to evaluate the effect of the interaction between this abnormal accumulation of sugar alcohol and the group variable (control/parasitism). The results revealed that this accumulation resulted in deficiency in the supply of specific sugars, which led to a lack of amino sugar and nucleotide sugar metabolism. Halting this metabolism could hamper pivotal functions in the plant host, including cell wall synthesis and lesion repair. In conclusion, our findings indicate that altered metabolic responses that occur during fungal parasitism can cause deficiency in substrates in pivotal pathways and thereby trigger pathological symptoms.
Topics: Amino Sugars; Basidiomycota; Chromatography, High Pressure Liquid; Fruit; Gas Chromatography-Mass Spectrometry; Host-Pathogen Interactions; Metabolic Networks and Pathways; Metabolome; Nucleotides; Plant Diseases; Plant Leaves; Rosaceae; Sugar Alcohols
PubMed: 27892480
DOI: 10.1038/srep37434 -
Nature Communications Aug 2018The means through which microbes and plants contribute to soil organic carbon (SOC) accumulation remain elusive due to challenges in disentangling the complex components...
The means through which microbes and plants contribute to soil organic carbon (SOC) accumulation remain elusive due to challenges in disentangling the complex components of SOC. Here we use amino sugars and lignin phenols as tracers for microbial necromass and plant lignin components, respectively, and investigate their distribution in the surface soils across Mongolian grasslands in comparison with published data for other grassland soils of the world. While lignin phenols decrease, amino sugars increase with SOC contents in all examined grassland soils, providing continental-scale evidence for the key role of microbial necromass in SOC accumulation. Moreover, in contrast to clay's control on amino sugar accumulation in fine-textured soils, aridity plays a central role in amino sugar accrual and lignin decomposition in the coarse-textured Mongolian soils. Hence, aridity shifts may have differential impacts on microbial-mediated SOC accumulation in grassland soils of varied textures.
Topics: Amino Sugars; Carbon Sequestration; Grassland; Lignin; Soil; Soil Microbiology
PubMed: 30154479
DOI: 10.1038/s41467-018-05891-1 -
Oncology 2023Correct tumor subtyping of primary renal tumors is essential for treatment decision in daily routine. Most of the tumors can be classified based on morphology alone....
BACKGROUND
Correct tumor subtyping of primary renal tumors is essential for treatment decision in daily routine. Most of the tumors can be classified based on morphology alone. Nevertheless, some diagnoses are difficult, and further investigations are needed for correct tumor subtyping. Besides histochemical investigations, high-mass-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can detect new diagnostic biomarkers and hence improve the diagnostic.
PATIENTS AND METHODS
Formalin-fixed paraffin embedded tissue specimens from clear cell renal cell carcinoma (ccRCC, n = 552), papillary renal cell carcinoma (pRCC, n = 122), chromophobe renal cell carcinoma (chRCC, n = 108), and renal oncocytoma (rO, n = 71) were analyzed by high-mass-resolution MALDI fourier-transform ion cyclotron resonance (FT-ICR) MSI. The SPACiAL pipeline was executed for automated co-registration of histological and molecular features. Pathway enrichment and pathway topology analysis were performed to determine significant differences between RCC subtypes.
RESULTS
We discriminated the four histological subtypes (ccRCC, pRCC, chRCC, and rO) and established the subtype-specific pathways and metabolic profiles. rO showed an enrichment of pentose phosphate, taurine and hypotaurine, glycerophospholipid, amino sugar and nucleotide sugar, fructose and mannose, glycine, serine, and threonine pathways. ChRCC is defined by enriched pathways including the amino sugar and nucleotide sugar, fructose and mannose, glycerophospholipid, taurine and hypotaurine, glycine, serine, and threonine pathways. Pyrimidine, amino sugar and nucleotide sugar, glycerophospholipids, and glutathione pathways are enriched in ccRCC. Furthermore, we detected enriched phosphatidylinositol and glycerophospholipid pathways in pRCC.
CONCLUSION
In summary, we performed a classification system with a mean accuracy in tumor discrimination of 85.13%. Furthermore, we detected tumor-specific biomarkers for the four most common primary renal tumors by MALDI-MSI. This method is a useful tool in differential diagnosis and biomarker detection.
Topics: Humans; Carcinoma, Renal Cell; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Mannose; Kidney Neoplasms; Taurine; Biomarkers, Tumor; Transcription Factors; Amino Sugars; Lasers
PubMed: 36198279
DOI: 10.1159/000526436 -
Journal of Biochemistry Jan 1996Galectins, animal lectins exhibiting specificity for galactosides, are now known to be widely distributed from lower invertebrates, such as sponges and nematodes, to... (Review)
Review
Galectins, animal lectins exhibiting specificity for galactosides, are now known to be widely distributed from lower invertebrates, such as sponges and nematodes, to higher vertebrates. The origin of the family can be traced back to the Precambrian era. They are classified into proto-, chimera-, and tandem-repeat types on the basis of protein architecture. The molecular functions of these types should be different because they can cross-link pairs of biomolecules of different combinations. Their biological significance, however, is not yet fully understood because they are involved in too many phenomena, such as differentiation, morphogenesis, metastasis, etc., and too many problems remain unsolved, such as those regarding their controversial cellular localization, mechanism of externalization, etc. Nevertheless, such difficulties seem to indicate their importance as household equipment and their common roles throughout the animal kingdom. They are likely to be responsible for recognizing the N-acetyllactosamine (LacNAc) structure, which is included in various glycoconjugates and considered to be an important glycocode, and then carry out appropriate tasks under given circumstances. Recently, crystallographic studies revealed that galectins and legume lectins such as concanavalin A have a common topology in spite of the absence of sequence homology. This suggests a possible relationship between animal and plant lectins, and the existence of a lectin super family. Studies on the galectin family are becoming increasingly important for glycobiology.
Topics: Amino Sugars; Animals; Carbohydrate Metabolism; Carbohydrates; Evolution, Molecular; Fabaceae; Humans; Lectins; Models, Molecular; Phylogeny; Plant Lectins; Plant Proteins; Plants, Medicinal
PubMed: 8907168
DOI: 10.1093/oxfordjournals.jbchem.a021192 -
The Journal of Antibiotics Nov 1974
Topics: Acetylation; Actinomycetales; Amino Sugars; Aminoglycosides; Antibiotics, Antineoplastic; Chemical Phenomena; Chemistry; Ethers; Hydrogenation; Hydrolysis; Methylation
PubMed: 4452659
DOI: 10.7164/antibiotics.27.866