-
1.
Communal living: glycan utilization by the human gut microbiota.
Briggs, JA, Grondin, JM, Brumer, H
Environmental microbiology. 2021;(1):15-35
Abstract
Our lower gastrointestinal tract plays host to a vast consortium of microbes, known as the human gut microbiota (HGM). The HGM thrives on a complex and diverse range of glycan structures from both dietary and host sources, the breakdown of which requires the concerted action of cohorts of carbohydrate-active enzymes (CAZymes), carbohydrate-binding proteins, and transporters. The glycan utilization profile of individual taxa, whether 'specialist' or 'generalist', is dictated by the number and functional diversity of these glycan utilization systems. Furthermore, taxa in the HGM may either compete or cooperate in glycan deconstruction, thereby creating a complex ecological web spanning diverse nutrient niches. As a result, our diet plays a central role in shaping the composition of the HGM. This review presents an overview of our current understanding of glycan utilization by the HGM on three levels: (i) molecular mechanisms of individual glycan deconstruction and uptake by key bacteria, (ii) glycan-mediated microbial interactions, and (iii) community-scale effects of dietary changes. Despite significant recent advancements, there remains much to be discovered regarding complex glycan metabolism in the HGM and its potential to affect positive health outcomes.
-
2.
Applications of emerging botanical hydrocolloids for edible films: A review.
Zibaei, R, Hasanvand, S, Hashami, Z, Roshandel, Z, Rouhi, M, Guimarães, JT, Mortazavian, AM, Sarlak, Z, Mohammadi, R
Carbohydrate polymers. 2021;:117554
Abstract
In recent years, many studies have been conducted on the production of edible films from emerging gums, which are mostly made from botanical sources. However, each one interacts differently with the film compounds, producing films with different properties that may improve or hinder their utilization in food packaging. Therefore, the aim of this review was to investigate and compare the physical, mechanical, thermal and structural properties of edible films produced with these emerging gums. The results of this review showed that it is possible to produce edible films with desirable physical, mechanical and thermal properties by optimizing the amounts and type of compounds in film formulations such as plasticizers, nanoparticles, lipid compounds, crosslinkers and combination of gums with other biopolymers. The future trends of this research include the deepening of knowledge to understand the molecular structures of emerging gums and to address the shortcomings of films based on these gums for their industrial-scale application in food packaging.
-
3.
Reducing Drought Stress in Plants by Encapsulating Plant Growth-Promoting Bacteria with Polysaccharides.
Saberi Riseh, R, Ebrahimi-Zarandi, M, Gholizadeh Vazvani, M, Skorik, YA
International journal of molecular sciences. 2021;(23)
Abstract
Drought is a major abiotic stress imposed by climate change that affects crop production and soil microbial functions. Plants respond to water deficits at the morphological, biochemical, and physiological levels, and invoke different adaptation mechanisms to tolerate drought stress. Plant growth-promoting bacteria (PGPB) can help to alleviate drought stress in plants through various strategies, including phytohormone production, the solubilization of mineral nutrients, and the production of 1-aminocyclopropane-1-carboxylate deaminase and osmolytes. However, PGPB populations and functions are influenced by adverse soil factors, such as drought. Therefore, maintaining the viability and stability of PGPB applied to arid soils requires that the PGPB have to be protected by suitable coatings. The encapsulation of PGPB is one of the newest and most efficient techniques for protecting beneficial bacteria against unfavorable soil conditions. Coatings made from polysaccharides, such as sodium alginate, chitosan, starch, cellulose, and their derivatives, can absorb and retain substantial amounts of water in the interstitial sites of their structures, thereby promoting bacterial survival and better plant growth.
-
4.
Study of fucoidans as natural biomolecules for therapeutical applications in osteoarthritis.
Vaamonde-García, C, Flórez-Fernández, N, Torres, MD, Lamas-Vázquez, MJ, Blanco, FJ, Domínguez, H, Meijide-Faílde, R
Carbohydrate polymers. 2021;:117692
Abstract
Osteoarthritis (OA) is the most prevalent articular chronic disease. Although, to date there is no cure for OA. Fucoidans, one of the main therapeutic components of brown algae, have emerged as promising molecules in OA treatment. However, the variability between fucoidans makes difficult the pursuit of the most suitable candidate to target specific pathological processes. By an in vitro experimental approach in chondrocytes and fibroblast-like synoviocytes, we observed that chemical composition of fucoidan, and specifically the phlorotannin content and the ratio sulfate:fucose, seems critically relevant for its biological activity. Nonetheless, other factors like concentration and molecular weight of the fucoidan may influence on its beneficial effects. Additionally, a cell-type dependent response was also detected. Thus, our results shed light on the potential use of fucoidans as natural molecules in the treatment of key pathological processes in the joint that favor the development of rheumatic disorders as OA.
-
5.
Transcriptional profiling of Pseudomonas aeruginosa PAO1 in response to anti-biofilm and anti-infection agent exopolysaccharide EPS273.
Wu, Z, Zheng, R, Zhang, J, Wu, S
Journal of applied microbiology. 2021;(1):265-277
Abstract
AIMS: Relatively, few anti-biofilm polysaccharides against Pseudomonas aeruginosa were done to investigate the underlying molecular mechanism. Exopolysaccharide EPS273 can clearly reduce biofilm formation and infection of P. aeruginosa. This study aims to investigate its anti-biofilm and anti-infection mechanism on transcriptional level. METHODS AND RESULTS Herein, we used an RNA-Seq transcriptomic approach to investigate the underlying anti-biofilm and anti-infection mechanism of EPS273. The expression levels of a large number of genes were changed after P. aeruginosa PAO1 was treated with EPS273. Especially, the genes related to biofilm formation, such as gene involved in production of extracellular matrix and virulence factor, genes involved in flagella and cell motility and genes involved in iron acquisition. Notably, the expression levels of genes involved in regulatory and signal transduction were markedly downregulated, such as two-component system PhoP-PhoQ and quorum sensing (QS) system LasI/LasR and RhlI/RhlR. Furthermore, when genes phoP and phoQ were disrupted, respectively, the reduction of biofilm formation and cell motility in mutant △phoP or △phoQ was also detected. CONCLUSION EPS273 may exert its anti-biofilm and anti-infection function by downregulating gene expression of two-component system PhoP-PhoQ and QS systems LasI/LasR and RhlI/RhlR of P. aeruginosa, which further regulated expression of genes involved in biofilm formation. SIGNIFICANCE AND IMPACT OF THE STUDY Our data will expand understanding of anti-biofilm mechanisms of polysaccharides on transcriptomic level.
-
6.
How Oxygen Binding Enhances Long-Range Electron Transfer: Lessons From Reduction of Lytic Polysaccharide Monooxygenases by Cellobiose Dehydrogenase.
Wang, Z, Feng, S, Rovira, C, Wang, B
Angewandte Chemie (International ed. in English). 2021;(5):2385-2392
Abstract
Long-range electron transfer (ET) in metalloenzymes is a general and fundamental process governing O2 activation and reduction. Lytic polysaccharide monooxygenases (LPMOs) are key enzymes for the oxidative cleavage of insoluble polysaccharides, but their reduction mechanism by cellobiose dehydrogenase (CDH), one of the most commonly used enzymatic electron donors, via long-range ET is still an enigma. Using multiscale simulations, we reveal that interprotein ET between CDH and LPMO is mediated by the heme propionates of CDH and solvent waters. We also show that oxygen binding to the copper center of LPMO is coupled with the long-range interprotein ET. This process, which is spin-regulated and enhanced by the presence of O2 , directly leads to LPMO-CuII -O2- , bypassing the formation of the generally assumed LPMO-CuI species. The uncovered ET mechanism rationalizes experimental observations and might have far-reaching implications for LPMO catalysis as well as the O2 - or CO-binding-enhanced long-range ET processes in other metalloenzymes.
-
7.
Policaptil Gel Retard in adult subjects with the metabolic syndrome: Efficacy, safety, and tolerability compared to metformin.
Guarino, G, Della Corte, T, Strollo, F, Gentile, S, ,
Diabetes & metabolic syndrome. 2021;(3):901-907
Abstract
BACKGROUND Policaptil Gel Retard® (PGR), is a new macromolecule complex based on polysaccharides slowing the rate of carbohydrate and fat absorption. It proved to significantly reduce body weight, acanthosis nigricans expression, HbA1c levels, and glucose metabolism abnormalities in obese, hyper-insulinemic adolescents. No such data are available for adults. AIM: to compare the effects of PGR vs. metformin in adult subjects with the Metabolic Syndrome (MS) and T2DM on a Low Glycemic Index diet. SUBJECTS AND METHODS This spontaneous clinical, longitudinal, single-blind, randomized study based on a per-protocol analysis enrolled 100 outpatients with MS and T2DM consecutively referring to our clinic for three months, and randomly assigned to either the active treatment (Group A:, 6 tablets/day) or the comparator (Group B: Metformin tablets, 1500-2000 mg/day in two divided doses during the two main meals, to minimize side effects) to be taken 30 min before each main meal in equally divided doses. Serum lipid profile, anthropometry, HOMA-IR index, and tolerability parameters were evaluated before and after a 6-month follow-up period. RESULTS all parameters improved at a similar rate in both groups but for the lipid profile, which got even better in Group A. Group A also experienced less prominent gastrointestinal side effects than its counterpart. CONCLUSION For the first time, we showed the non-inferiority of PGR compared to metformin in obese adult subjects with the MS and T2DM as for glycemic control and a clear-cut superiority of PGR in terms of both serum lipid-lowering capacity and tolerability.
-
8.
Computer-aided engineering of a branching sucrase for the glucodiversification of a tetrasaccharide precursor of S. flexneri antigenic oligosaccharides.
Benkoulouche, M, Ben Imeddourene, A, Barel, LA, Lefebvre, D, Fanuel, M, Rogniaux, H, Ropartz, D, Barbe, S, Guieysse, D, Mulard, LA, et al
Scientific reports. 2021;(1):20294
Abstract
Enzyme engineering approaches have allowed to extend the collection of enzymatic tools available for synthetic purposes. However, controlling the regioselectivity of the reaction remains challenging, in particular when dealing with carbohydrates bearing numerous reactive hydroxyl groups as substrates. Here, we used a computer-aided design framework to engineer the active site of a sucrose-active [Formula: see text]-transglucosylase for the 1,2-cis-glucosylation of a lightly protected chemically synthesized tetrasaccharide, a common precursor for the synthesis of serotype-specific S. flexneri O-antigen fragments. By targeting 27 amino acid positions of the acceptor binding subsites of a GH70 branching sucrase, we used a RosettaDesign-based approach to propose 49 mutants containing up to 15 mutations scattered over the active site. Upon experimental evaluation, these mutants were found to produce up to six distinct pentasaccharides, whereas only two were synthesized by the parental enzyme. Interestingly, we showed that by introducing specific mutations in the active site of a same enzyme scaffold, it is possible to control the regiospecificity of the 1,2-cis glucosylation of the tetrasaccharide acceptor and produce a unique diversity of pentasaccharide bricks. This work offers novel opportunities for the development of highly convergent chemo-enzymatic routes toward S. flexneri haptens.
-
9.
N-glycan-mediated shielding of ADAMTS13 prevents binding of pathogenic autoantibodies in immune-mediated TTP.
Ercig, B, Graça, NAG, Kangro, K, Arfman, T, Wichapong, K, Hrdinová, J, Kaijen, P, van Alphen, FPJ, van den Biggelaar, M, Vanhoorelbeke, K, et al
Blood. 2021;(19):2694-2698
-
-
Free full text
-
Abstract
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is an autoimmune disorder caused by the development of autoantibodies targeting different domains of ADAMTS13. Profiling studies have shown that residues R568, F592, R660, Y661, and Y665 within exosite-3 of the spacer domain provide an immunodominant region of ADAMTS13 for pathogenic autoantibodies that develop in patients with iTTP. Modification of these 5 core residues with the goal of reducing autoantibody binding revealed a significant tradeoff between autoantibody resistance and proteolytic activity. Here, we employed structural bioinformatics to identify a larger epitope landscape on the ADAMTS13 spacer domain. Models of spacer-antibody complexes predicted that residues R568, L591, F592, K608, M609, R636, L637, R639, R660, Y661, Y665, and L668 contribute to an expanded epitope within the spacer domain. Based on bioinformatics-guided predictions, we designed a panel of N-glycan insertions in this expanded epitope to reduce the binding of spacer domain autoantibodies. One N-glycan variant (NGLY3-ADAMTS13, containing a K608N substitution) showed strongly reduced reactivity with TTP patient sera (28%) as compared with WT-ADAMTS13 (100%). Insertion of an N-glycan at amino acid position 608 did not interfere with processing of von Willebrand factor, positioning the resulting NGLY3-ADAMTS13 variant as a potential novel therapeutic option for treatment of iTTP.
-
10.
Stimuli-responsive natural gums-based drug delivery systems for cancer treatment.
Soleimani, K, Derakhshankhah, H, Jaymand, M, Samadian, H
Carbohydrate polymers. 2021;:117422
Abstract
Chemotherapy as the main cancer treatment method has non-specific effects and various side-effects. Accordingly, significant attempts have been conducted to enhance its efficacy through design and development of "smart" drug delivery systems (DDSs). In this context, natural gums, as a nice gift by the nature, can be exploited as stimuli-responsive DDSs for cancer treatment in part due to their renewability, availability, low cost, bioactivity, biocompatibility, low immunogenicity, biodegradability, and acceptable stability in both in vitro and in vivo conditions. However, some shortcomings (e.g., poor mechanical properties and high hydration rate) restrict their biomedical application ranges that can be circumvented through modification process (e.g., grafting of stimuli-responsive polymers or small molecules) to obtain tailored biomaterials. This review article aimed to compile the stimuli-responsive DDSs based on natural gums. In addition, different types of stimuli, the fundamental features of natural gums, as well as their chemical modification approaches are also shortly highlighted.