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Applied Microbiology and Biotechnology Oct 2019Glucosamine (GlcN) is an amine sugar, in which a hydroxyl group of glucose is replaced with an amino group. It is an important part of the polysaccharides chitin and... (Review)
Review
Glucosamine (GlcN) is an amine sugar, in which a hydroxyl group of glucose is replaced with an amino group. It is an important part of the polysaccharides chitin and chitosan and is highly hydrophilic. It is also an important compound required for the formation of cartilage cells and represents one of the elementary units of the cartilage matrix and joint fluid. GlcN has been widely used in food, cosmetics, health care, and pharmaceutical industries. This paper fully addresses the categories and biomanufacturing methods of GlcN, including its production by fermentation with wild-type as well as engineered microorganisms and enzymatic catalysis with a series of chitinolytic enzymes. However, GlcN is usually produced from glucose by fermentation in a coupled manner with N-acetylglucosamine (GlcNAc). Enzymatic catalysis is thus a specific pathway for production of GlcN where chitin can be directly hydrolyzed to GlcN. In industry, GlcN produced with fungal mycelium as raw materials (plant GlcN) is thought as a high-end product because of vegetarian and non-transgenosis. In our opinion, more studies should be performed in order to develop a competitive enzymatic pathway using Aspergillus niger mycelium for the preparation of high-end GlcN.
Topics: Aspergillus niger; Biocatalysis; Fermentation; Glucosamine; Industrial Microbiology; Metabolic Networks and Pathways; Mycelium
PubMed: 31440792
DOI: 10.1007/s00253-019-10084-x -
Biomaterials Science Apr 2023Sialic acid is a kind of monosaccharide expressed on the non-reducing end of glycoproteins or glycolipids. It acts as a signal molecule combining with its natural... (Review)
Review
Sialic acid is a kind of monosaccharide expressed on the non-reducing end of glycoproteins or glycolipids. It acts as a signal molecule combining with its natural receptors such as selectins and siglecs (sialic acid-binding immunoglobulin-like lectins) in intercellular interactions like immunological surveillance and leukocyte infiltration. The last few decades have witnessed the exploration of the roles that sialic acid plays in different physiological and pathological processes and the use of sialic acid-modified materials as therapeutics for related diseases like immune dysregulation and virus infection. In this review, we will briefly introduce the biomedical function of sialic acids in organisms and the utilization of multivalent sialic acid materials for targeted drug delivery as well as therapeutic applications including anti-inflammation and anti-virus.
Topics: N-Acetylneuraminic Acid; Sialic Acid Binding Immunoglobulin-like Lectins; Sialic Acids; Glycoproteins; Leukocytes
PubMed: 36661319
DOI: 10.1039/d2bm01595a -
International Journal of Molecular... Oct 2020The so-called "" has become an attractive research area, as an increasing number of natural products containing a sialic acid moiety have been shown to play important... (Review)
Review
The so-called "" has become an attractive research area, as an increasing number of natural products containing a sialic acid moiety have been shown to play important roles in biological, pathological, and immunological processes. The intramolecular lactones of sialic acids are a subclass from this crucial family that could have central functions in the discrimination of physiological and pathological conditions. In this review, we report an in-depth analysis of the synthetic achievements in the preparation of the intramolecular lactones of sialic acids (1,4-, 1,7- and γ-lactones), in their free and/or protected form. In particular, recent advances in the synthesis of the 1,7-lactones have allowed the preparation of key sialic acid derivatives. These compounds could be used as authentic reference standards for their correct determination in biological samples, thus overcoming some of the limitations of the previous analytical procedures.
Topics: Lactones; Sialic Acids
PubMed: 33143039
DOI: 10.3390/ijms21218098 -
Nature Sep 2022Bacterial cell wall components provide various unique molecular structures that are detected by pattern recognition receptors (PRRs) of the innate immune system as...
Bacterial cell wall components provide various unique molecular structures that are detected by pattern recognition receptors (PRRs) of the innate immune system as non-self. Most bacterial species form a cell wall that consists of peptidoglycan (PGN), a polymeric structure comprising alternating amino sugars that form strands cross-linked by short peptides. Muramyl dipeptide (MDP) has been well documented as a minimal immunogenic component of peptidoglycan. MDP is sensed by the cytosolic nucleotide-binding oligomerization domain-containing protein 2 (NOD2). Upon engagement, it triggers pro-inflammatory gene expression, and this functionality is of critical importance in maintaining a healthy intestinal barrier function. Here, using a forward genetic screen to identify factors required for MDP detection, we identified N-acetylglucosamine kinase (NAGK) as being essential for the immunostimulatory activity of MDP. NAGK is broadly expressed in immune cells and has previously been described to contribute to the hexosamine biosynthetic salvage pathway. Mechanistically, NAGK functions upstream of NOD2 by directly phosphorylating the N-acetylmuramic acid moiety of MDP at the hydroxyl group of its C6 position, yielding 6-O-phospho-MDP. NAGK-phosphorylated MDP-but not unmodified MDP-constitutes an agonist for NOD2. Macrophages from mice deficient in NAGK are completely deficient in MDP sensing. These results reveal a link between amino sugar metabolism and innate immunity to bacterial cell walls.
Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Bacteria; Cell Wall; Hexosamines; Immunity, Innate; Macrophages; Mice; Nod2 Signaling Adaptor Protein; Peptidoglycan; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor)
PubMed: 36002575
DOI: 10.1038/s41586-022-05125-x -
Methods (San Diego, Calif.) Mar 2023Self-supervised learning has shown superior performance on graph-related tasks in recent years. The most advanced methods are based on contrast learning, which severely...
Self-supervised learning has shown superior performance on graph-related tasks in recent years. The most advanced methods are based on contrast learning, which severely limited by structured data augmentation techniques and complex training methods. Generative self-supervised learning, especially graph autoencoders (GAEs), can prevent the above dependence and has been demonstrated as an effective approach. In addition, most previous works only reconstruct the graph topological structure or node features. Few works consider both and combine them together to obtain their complementary information. To overcome these problems, we propose a generative self-supervised graph representation learning methodology named Multi-View Dual-decoder Graph Autoencoder (MDGA). Specifically, we first design a multi-sample graph learning strategy which benefits the generalization of the dual-decoder graph autoencoder. Moreover, the proposed model reconstructs the graph topological structure with a traditional GAE and extracts node attributes by masked feature reconstruction. Experimental results on five public benchmark datasets demonstrate that MDGA outperforms state-of-the-art methods in both node classification and link prediction tasks.
Topics: Benchmarking; Dansyl Compounds; Galactosamine
PubMed: 36792041
DOI: 10.1016/j.ymeth.2023.02.002 -
Advances in Carbohydrate Chemistry and... 20231-Amino-1-deoxy-d-fructose (fructosamine, FN) derivatives are omnipresent in all living organisms, as a result of non-enzymatic condensation and Amadori rearrangement...
1-Amino-1-deoxy-d-fructose (fructosamine, FN) derivatives are omnipresent in all living organisms, as a result of non-enzymatic condensation and Amadori rearrangement reactions between free glucose and biogenic amines such as amino acids, polypeptides, or aminophospholipids. Over decades, steady interest in fructosamine was largely sustained by its role as a key intermediate structure in the Maillard reaction that is responsible for the organoleptic and nutritional value of thermally processed foods, and for pathophysiological effects of hyperglycemia in diabetes. New trends in fructosamine research include the discovery and engineering of FN-processing enzymes, development of advanced tools for hyperglycemia monitoring, and evaluation of the therapeutic potential of both fructosamines and FN-recognizing proteins. This article covers developments in the field of fructosamine and its derivatives since 2010 and attempts to ascertain challenges in future research.
Topics: Humans; Fructosamine; Fructose; Amino Acids; Proteins; Hyperglycemia
PubMed: 37968036
DOI: 10.1016/bs.accb.2023.10.001 -
Chemical Reviews Feb 2021Protein O-linked β--acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is a unique monosaccharide modification discovered in the early 1980s. With the... (Review)
Review
Protein O-linked β--acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is a unique monosaccharide modification discovered in the early 1980s. With the technological advances in the past several decades, great progress has been made to reveal the biochemistry of O-GlcNAcylation, the substrates of O-GlcNAcylation, and the functional importance of protein O-GlcNAcylation. As a nutrient sensor, protein O-GlcNAcylation plays important roles in almost all biochemical processes examined. Although the functional importance of O-GlcNAcylation of proteins has been extensively reviewed previously, the chemical and biochemical aspects have not been fully addressed. In this review, by critically evaluating key publications in the past 35 years, we aim to provide a comprehensive understanding of this important post-translational modification (PTM) from analytical and biochemical perspectives. Specifically, we will cover (1) multiple analytical advances in the characterization of O-GlcNAc cycling components (i.e., the substrate donor UDP-GlcNAc, the two key enzymes O-GlcNAc transferase and O-GlcNAcase, and O-GlcNAc substrate proteins), (2) the biochemical characterization of the enzymes with a variety of chemical tools, and (3) exploration of O-GlcNAc cycling and its modulating chemicals as potential biomarkers and therapeutic drugs for diseases. Last but not least, we will discuss the challenges and possible solutions for basic and translational research of protein O-GlcNAcylation in the future.
Topics: Acetylglucosamine; Humans; N-Acetylglucosaminyltransferases; beta-N-Acetylhexosaminidases
PubMed: 33416322
DOI: 10.1021/acs.chemrev.0c00884 -
BMC Biology Jul 2019Altered metabolism and deregulated cellular energetics are now considered a hallmark of all cancers. Glucose, glutamine, fatty acids, and amino acids are the primary... (Review)
Review
Altered metabolism and deregulated cellular energetics are now considered a hallmark of all cancers. Glucose, glutamine, fatty acids, and amino acids are the primary drivers of tumor growth and act as substrates for the hexosamine biosynthetic pathway (HBP). The HBP culminates in the production of an amino sugar uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) that, along with other charged nucleotide sugars, serves as the basis for biosynthesis of glycoproteins and other glycoconjugates. These nutrient-driven post-translational modifications are highly altered in cancer and regulate protein functions in various cancer-associated processes. In this review, we discuss recent progress in understanding the mechanistic relationship between the HBP and cancer.
Topics: Biosynthetic Pathways; Hexosamines; Neoplasms; Protein Processing, Post-Translational; Proteins
PubMed: 31272438
DOI: 10.1186/s12915-019-0671-3 -
Advances in Carbohydrate Chemistry and... 2022The synthesis of sialic acid-containing molecules has posed a formidable challenge to carbohydrate chemists for over 50 years. Our research group has intensively...
The synthesis of sialic acid-containing molecules has posed a formidable challenge to carbohydrate chemists for over 50 years. Our research group has intensively searched for robust chemistry to enable the construction of a broad spectrum of sialic acid-containing molecules to advance the understanding and application of their biological functions. Herein, we describe our research findings on the development of sialic acid donors for α-selective glycosidation and the chemical synthesis of sialic acid- containing molecules, with a special focus on gangliosides and their fluorescent probes.
Topics: Sialic Acids; N-Acetylneuraminic Acid; Gangliosides; Carbohydrates; Fluorescent Dyes
PubMed: 36435533
DOI: 10.1016/bs.accb.2022.09.003 -
Neuro-oncology Nov 2023In glioblastoma (GBM), the effects of altered glycocalyx are largely unexplored. The terminal moiety of cell coating glycans, sialic acid, is of paramount importance for...
BACKGROUND
In glioblastoma (GBM), the effects of altered glycocalyx are largely unexplored. The terminal moiety of cell coating glycans, sialic acid, is of paramount importance for cell-cell contacts. However, sialic acid turnover in gliomas and its impact on tumor networks remain unknown.
METHODS
We streamlined an experimental setup using organotypic human brain slice cultures as a framework for exploring brain glycobiology, including metabolic labeling of sialic acid moieties and quantification of glycocalyx changes. By live, 2-photon and high-resolution microscopy we have examined morphological and functional effects of altered sialic acid metabolism in GBM. By calcium imaging we investigated the effects of the altered glycocalyx on a functional level of GBM networks.
RESULTS
The visualization and quantitative analysis of newly synthesized sialic acids revealed a high rate of de novo sialylation in GBM cells. Sialyltrasferases and sialidases were highly expressed in GBM, indicating that significant turnover of sialic acids is involved in GBM pathology. Inhibition of either sialic acid biosynthesis or desialylation affected the pattern of tumor growth and lead to the alterations in the connectivity of glioblastoma cells network.
CONCLUSIONS
Our results indicate that sialic acid is essential for the establishment of GBM tumor and its cellular network. They highlight the importance of sialic acid for glioblastoma pathology and suggest that dynamics of sialylation have the potential to be targeted therapeutically.
Topics: Humans; Glioblastoma; N-Acetylneuraminic Acid; Sialic Acids; Signal Transduction; Brain Neoplasms; Cell Line, Tumor
PubMed: 37288604
DOI: 10.1093/neuonc/noad101