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Carbohydrate Research Oct 2021Bottom-up synthesis of β-glucans such as callose, fungal β-(1,3)(1,6)-glucan and cellulose, can create the defined compounds that are needed to perform fundamental... (Review)
Review
Bottom-up synthesis of β-glucans such as callose, fungal β-(1,3)(1,6)-glucan and cellulose, can create the defined compounds that are needed to perform fundamental studies on glucan properties and develop applications. With the importance of β-glucans and cellulose in high-profile fields such as nutrition, renewables-based biotechnology and materials science, the enzymatic synthesis of such relevant carbohydrates and their derivatives has attracted much attention. Here we review recent developments in enzymatic synthesis of β-glucans and cellulose, with a focus on progress made over the last five years. We cover the different types of biocatalysts employed, their incorporation in cascades, the exploitation of enzyme promiscuity and their engineering, and reaction conditions affecting the production as well as in situ self-assembly of (non)functionalised glucans. The recent achievements in the application of glycosyl transferases and β-1,4- and β-1,3-glucan phosphorylases demonstrate the high potential and versatility of these biocatalysts in glucan synthesis in both industrial and academic contexts.
Topics: Cellulose; Phosphorylases; beta-Glucans
PubMed: 34392134
DOI: 10.1016/j.carres.2021.108411 -
Molecules (Basel, Switzerland) Jul 2022β-glucans are known as biological response modifiers. However, different sources can result in structural differences and as a result differences in their biological...
β-glucans are known as biological response modifiers. However, different sources can result in structural differences and as a result differences in their biological activity. The hot water extraction method allows to obtain, high molecular weight β-glucans without altering their structure by using strong chemicals, such as alkalis or acids. Analysis of β-glucans by FT-IR and NMR spectroscopy in solid state is superior to analysis in solution as it allows researchers to study the preserved structure of the extracted polysaccharides. FT-IR spectroscopy was used in this study to make side-by-side comparison analysis of hot water extracted β-glucans from different yeast sources. NMR spectroscopy was used to confirm findings made by FT-IR spectroscopy. Extracted β-glucans exhibit characteristic structure of β-1,3/1,6-linked glucans with noticeable levels of proteins, possibly in a form of oligopeptides, chitin and other impurities. β-glucans obtained from , and exhibited higher protein content. Differences in mannan, chitin and α-glucan content were also observed; however, the species-specific structure of obtained β-glucans could not be confirmed without additional studies. Structural analysis of high molecular weight β-glucans in solid state by FT-IR spectroscopy is difficult or limited due to band intensity changes and overlapping originating from different molecules.
Topics: Chitin; Glucans; Saccharomyces cerevisiae; Spectroscopy, Fourier Transform Infrared; Water; beta-Glucans
PubMed: 35889491
DOI: 10.3390/molecules27144616 -
Nutrients Apr 2021The importance of a well-functioning and balanced immune system has become more apparent in recent decades. Various elements have however not yet been uncovered as... (Review)
Review
The importance of a well-functioning and balanced immune system has become more apparent in recent decades. Various elements have however not yet been uncovered as shown, for example, in the uncertainty on immune system responses to COVID-19. Fungal beta-glucans are bioactive molecules with immunomodulating properties. Insights into the effects and function of beta-glucans, which have been used in traditional Chinese medicine for centuries, advances with the help of modern immunological and biotechnological methods. However, it is still unclear into which area beta-glucans fit best: supplements or medicine? This review has highlighted the potential application of fungal beta-glucans in nutrition and medicine, reviewing their formulation, efficacy, safety profile, and immunomodulating effects. The current status of dietary fungal glucans with respect to the European scientific requirements for health claims related to the immune system and defense against pathogens has been reviewed. Comparing the evidence base of the putative health effects of fungal beta-glucan supplements with the published guidance documents by EFSA on substantiating immune stimulation and pathogen defense by food products shows that fungal beta-glucans could play a role in supporting and maintaining health and, thus, can be seen as a good health-promoting substance from food, which could mean that this effect may also be claimed if approved. In addition to these developments related to food uses of beta-glucan-containing supplements, beta-glucans could also hold a novel position in Western medicine as the concept of trained immunity is relatively new and has not been investigated to a large extent. These innovative concepts, together with the emerging success of modern immunological and biotechnological methods, suggest that fungal glucans may play a promising role in both perspectives, and that there are possibilities for traditional medicine to provide an immunological application in both medicine and nutrition.
Topics: Adolescent; Adult; Agaricales; Aged; Animals; COVID-19; Diet; Dietary Supplements; Female; Fungal Polysaccharides; Fungi; Humans; Immune System; Immunity; Immunomodulation; Infant; Infant, Newborn; Male; Middle Aged; Pleurotus; SARS-CoV-2; Saccharomyces cerevisiae; Young Adult; beta-Glucans
PubMed: 33920583
DOI: 10.3390/nu13041333 -
European Journal of Immunology Apr 2021Intestinal epithelial cells (IECs) are the first to encounter luminal antigens and play an active role in intestinal immune responses. We previously reported that...
Intestinal epithelial cells (IECs) are the first to encounter luminal antigens and play an active role in intestinal immune responses. We previously reported that β-glucans, major fungal cell-wall glycans, induced chemokine secretion by IEC lines in a Dectin-1- and Syk-dependent manner. Here, we show that in contrast to β-glucans, stimulation of IEC lines with Candida albicans and Saccharomyces cerevisiae did not induce secretion of any of the proinflammatory cytokines IL-8, CCL2, CXCL1, and GM-CSF. Commensal fungi and β-glucans activated Syk and ERK in IEC lines. However, only β-glucans activated p38, JNK, and the transcription factors NF-κB p65 and c-JUN, which were necessary for cytokine secretion. Furthermore, costimulation of IEC lines with β-glucans and C. albicans yielded decreased cytokine secretion compared to stimulation with β-glucans alone. Finally, ex vivo stimulation of human colonic mucosal explants with zymosan and C. albicans, leads to epithelial Syk and ERK phosphorylation, implying recognition of fungi and similar initial signaling pathways as in IEC lines. Lack of cytokine secretion in response to commensal fungi may reflect IECs' response to fungal glycans, other than β-glucans, that contribute to mucosal tolerance. Skewed epithelial response to commensal fungi may impair homeostasis and contribute to intestinal inflammation.
Topics: Caco-2 Cells; Candida albicans; Cell Line, Tumor; Cell Wall; Cytokines; Epithelial Cells; Extracellular Signal-Regulated MAP Kinases; HT29 Cells; Host-Pathogen Interactions; Humans; Intestinal Mucosa; Phosphorylation; Syk Kinase; Zymosan; beta-Glucans
PubMed: 33616974
DOI: 10.1002/eji.202048852 -
Drug Metabolism and Pharmacokinetics Feb 2022Schizophyllan (SPG), a member of the β-glucan family, can form novel complexes with homo-polynucleotides such as poly(dA) through hydrogen bonding between two main... (Review)
Review
Schizophyllan (SPG), a member of the β-glucan family, can form novel complexes with homo-polynucleotides such as poly(dA) through hydrogen bonding between two main chain glucoses and the one nucleotide base. Dectin-1, one of the major receptors for β-glucans, is known to be expressed on antigen presenting cells (APCs) such as macrophages and dendritic cells. This suggests that the above-mentioned complexes could deliver bound functional oligonucleotides (ODNs) including antisense (AS)-ODNs, small interfering RNA, and CpG-ODNs to the APCs. Analysis using a quartz crystal microbalance revealed that a complex consisting of SPG and dA with a phosphorothioate backbone was recognized by recombinant Dectin-1 protein. Treatment with this complex containing an AS-ODN for tumor necrosis factor alpha protected mice against lipopolysaccharide-induced hepatitis at a very low AS-ODN dose. Moreover, immunization with CpG-ODN/SPG complex and antigenic proteins induced potent antigen specific immune responses. The present review also represents peptide delivery by conjugation with dA and the preparation of a nanogel using DNA-DNA hybridization. These findings indicate that the delivery of a specific ODN using β-glucans could be used for treating various diseases caused by APCs and for activating antigen specific immune responses.
Topics: Animals; Antigen-Presenting Cells; Mice; Oligonucleotides; RNA, Small Interfering; Sizofiran; beta-Glucans
PubMed: 34896749
DOI: 10.1016/j.dmpk.2021.100434 -
Nutrition Journal Apr 2014Beta-glucans are a heterogeneous group of natural polysaccharides mostly investigated for their immunological effects. Due to the low systemic availability of oral... (Review)
Review
Beta-glucans are a heterogeneous group of natural polysaccharides mostly investigated for their immunological effects. Due to the low systemic availability of oral preparations, it has been thought that only parenterally applied beta-glucans can modulate the immune system. However, several in vivo and in vitro investigations have revealed that orally applied beta-glucans also exert such effects. Various receptor interactions, explaining possible mode of actions, have been detected. The effects mainly depend on the source and structure of the beta-glucans. In the meantime, several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect.
Topics: Animals; Common Cold; Humans; Immunologic Factors; Rats; beta-Glucans
PubMed: 24774968
DOI: 10.1186/1475-2891-13-38 -
Molecules (Basel, Switzerland) Apr 2020The search for lipid-lowering drugs is important for clinical medicine. This review summarizes our research findings regarding the hypolipidemic activity of... (Review)
Review
The search for lipid-lowering drugs is important for clinical medicine. This review summarizes our research findings regarding the hypolipidemic activity of polysaccharides. There are several validated agents altering lipid levels which reduce the risk of atherosclerotic cardiovascular events. Nonetheless, for many people, the risk of such an event remains unacceptably high despite treatment with these agents. This situation has prompted the search for new therapies to reduce the residual cardiovascular risk. The lipid-lowering effect of β-glucans consumed with food was demonstrated in patients with atherosclerosis. The mechanism of the protective effect of β-glucans is poorly studied. The effects of β-glucans are mediated by Toll-like receptors, by dectin-1, and possibly by other receptors. Nevertheless, the mechanism of the protective action of β-glucan in lipemic mice has been studied insufficiently. This review will present up-to-date information regarding experimental hypolipidemic polysaccharide compounds that hold promise for medicine. Phagocyte-specific chitotriosidase in humans contributes to innate immune responses against chitin-containing fungi. This enzyme has been first described in patients with Gaucher disease and serves as an important diagnostic biomarker. It has been reported that, in mice, chitin particles of certain size are recognized by macrophages through Toll-like receptors, dectin-1, and to a lesser extent through mannose receptor.
Topics: Gene Expression Regulation; Gene Regulatory Networks; Hexosaminidases; Humans; Hyperlipidemias; Hypolipidemic Agents; Lectins, C-Type; Mannans; Polysaccharides; Toll-Like Receptors; beta-Glucans
PubMed: 32316136
DOI: 10.3390/molecules25081819 -
Molecules (Basel, Switzerland) Nov 2019The cell walls of fungi are composed of glycoproteins, chitin, and α- and β-glucans. Although there are many reports on β-glucans, α-glucan polysaccharides are not... (Review)
Review
The cell walls of fungi are composed of glycoproteins, chitin, and α- and β-glucans. Although there are many reports on β-glucans, α-glucan polysaccharides are not yet fully understood. This review characterizes the physicochemical properties and functions of (1→3)-α-d-glucans. Particular attention has been paid to practical application and the effect of glucans in various respects, taking into account unfavourable effects and potential use. The role of α-glucans in plant infection has been proven, and collected facts have confirmed the characteristics of infection associated with the presence of glucan in fungal cell wall. Like β-glucans, there are now evidence that α-glucans can also stimulate the immune system. Moreover, α-d-glucans have the ability to induce mutanases and can thus decompose plaque.
Topics: Aspergillosis; Aspergillus fumigatus; Cell Wall; Chitin; Fungi; Glucans; Glycoproteins; Plant Diseases; Polysaccharides; beta-Glucans
PubMed: 31684030
DOI: 10.3390/molecules24213972 -
International Journal of Molecular... Feb 2021β-Glucan is widely distributed in various plants and microorganisms and is composed of β-1,3-linked d-glucose units. It may have a branched short or long side chain of...
β-Glucan is widely distributed in various plants and microorganisms and is composed of β-1,3-linked d-glucose units. It may have a branched short or long side chain of glucose units with β-1,6- or β-1,4-linkage. Numerous studies have investigated different β-glucans and revealed their bioactivities. To understand the structure-function relationship of β-glucan, we constructed a split-luciferase complementation assay for the structural analysis of long-chain β-1,6-branched β-1,3-glucan. The N- and C-terminal fragments of luciferase from deep-sea shrimp were fused to insect-derived β-1,3-glucan recognition protein and fungal endo-β-1,6-glucanase (Neg1)-derived β-1,6-glucan recognition protein, respectively. In this approach, two β-glucan recognition proteins bound to β-glucan molecules come into close proximity, resulting in the assembly of the full-length reporter enzyme and induction of transient luciferase activity, indicative of the structure of β-glucan. To test the applicability of this assay, β-glucan and two β-glucan recognition proteins were mixed, resulting in an increase in the luminescence intensity in a β-1,3-glucan with a long polymer of β-1,6-glucan in a dose-dependent manner. This simple test also allows the monitoring of real-time changes in the side chain structure and serves as a convenient method to distinguish between β-1,3-glucan and long-chain β-1,6-branched β-1,3-glucan in various soluble and insoluble β-glucans.
Topics: Animals; Biosensing Techniques; Cell Wall; Glycoside Hydrolases; Luciferases; Substrate Specificity; beta-Glucans
PubMed: 33557290
DOI: 10.3390/ijms22041576 -
Frontiers in Immunology 2023β-Glucans are a group of heterogeneous glucose polymers that possess immunomodulatory activities. The complex nature of their structures, uncertainty regarding the...
β-Glucans are a group of heterogeneous glucose polymers that possess immunomodulatory activities. The complex nature of their structures, uncertainty regarding the doses, and variable immune effects pose a challenge to comprehensive understanding. In this study, we investigated the immune responses and apoptosis effects in Nile tilapia () head kidney macrophages (MФ) upon exposure to two β-Glucans (Paramylon and Laminarin) at low and high doses. Our results demonstrate that Paramylon elicits more robust immune responses than Laminarin, albeit with a dose-limiting effect. We also observed that the high-dose Paramylon induces apoptosis, whereas no such effect was detected in Laminarin treatment. Mechanistically, high-dose Paramylon activates the intrinsic apoptosis pathway, with significantly up-regulation of intrinsic apoptosis-related genes and impaired mitochondrial function. On the other hand, Laminarin triggers metabolic reprogramming in MФ, resulting in the enrichment of the metabolite α-Ketoglutarate, which protects the MФ from apoptosis. Overall, our findings highlight the importance of identifying the optimal dose range for β-Glucans, based on sources or structures, to achieve maximal immunomodulatory effects. These results have important implications for the design and optimization of β-Glucans-based drugs or adjuvants in immunotherapies.
Topics: Animals; beta-Glucans; Immunomodulation; Immunotherapy; Apoptosis; Cichlids; Dust; Macrophages
PubMed: 37675105
DOI: 10.3389/fimmu.2023.1243358