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•Metabolic engineering of heparosan, heparin and heparan sulfate•Chemical and chemoenzymatic synthesis of low molecular weight heparins•Development of new heparin products
Heparin is ...a naturally occurring glycosaminoglycan from livestock, principally porcine intestine, and is clinically used as an anticoagulant drug. A limitation to heparin production is that it depends on a single animal species and potential problems have been associated with animal-derived heparin. The contamination crisis in 2008 led to a search for new animal sources and the investigation of non-animal sources of heparin. Over the past 5 years, new animal sources, chemical, and chemoenzymatic methods have been introduced to prepare heparin-based drugs. In this review, we describe advances in the preparation and synthesis of heparin and related products.
We review recent advances in the field of preparation and synthesis of indispensable anticoagulant drugs, heparin, and related products.
•A novel polysaccharide (PUP80S1) was obtained from Polyporus umbellatus sclerotia.•Structure characterization of PUP80S1 containing uronic acid was elucidated by NMR.•Globular chain conformation of ...PUP80S1 was determined by Atomic force microscopy.•Antioxidant activity of two polysaccharides having similar structure were compared.
Polyporus umbellatus is a medicinal fungus, has been used in traditional Chinese medicine for thousands years for treatment of edema, scanty urine, vaginal discharge, jaundice and diarrhea. The structure of a soluble polysaccharide (named PUP80S1), purified from the sclerotia of Polyporus umbellatus was elucidated by gas chromatography (GC), GC–mass spectrometry and nuclear magnetic resonance spectroscopy. PUP80S1 is a branched polysaccharide containing approximately 8.5% uronic acid and having an average molecular weight of 8.8kDa. Atomic force microscopy of PUP80S1 reveals a globular chain conformation in water. Antioxidant tests, Oxygen radical absorption capacity and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays indicate that PUP80S1 possesses significant antioxidant activity. But the related polysaccharide, PUP60S2, which contains more uronic acid residues and a higher level of branching, shows better antioxidant activity. These results suggest that structure features of polysaccharides play an important role in their physiological functions.
Glycosaminoglycans in infectious disease Kamhi, Eyal; Joo, Eun Ji; Dordick, Jonathan S. ...
Biological reviews of the Cambridge Philosophical Society,
November 2013, Letnik:
88, Številka:
4
Journal Article
Recenzirano
ABSTRACT
Glycosaminoglycans (GAGs) are complex carbohydrates that are ubiquitously present on the cell surface and in the extracellular matrix. Interactions between GAGs and pathogens represent the ...first line of contact between pathogen and host cell and are crucial to a pathogen's invasive potential. Their complexity and structural diversity allow GAGs to control a wide array of biological interactions influencing many physiological and pathological processes, including adhesion, cell‐to‐cell communication, biochemical cascades, and the immune response. In recent years, increasing evidence indicates an extraordinary role for GAGs in the pathogenesis of viruses, bacteria and parasites. Herein, we examine the interface between GAGs and different pathogens, and address the divergent biological functions of GAGs in infectious disease. We consider approaches to use this understanding to design novel therapeutic strategies addressing new challenges in the treatment of infectious diseases.
Lignocellulose represents a key sustainable source of biomass for transformation into biofuels and bio-based products. Unfortunately, lignocellulosic biomass is highly recalcitrant to ...biotransformation, both microbial and enzymatic, which limits its use and prevents economically viable conversion into value-added products. As a result, effective pretreatment strategies are necessary, which invariably involves high energy processing or results in the degradation of key components of lignocellulose. In this work, the ionic liquid, 1-ethyl-3-methylimidazolium acetate (EmimCH₃COO), was used as a pretreatment solvent to extract lignin from wood flour. The cellulose in the pretreated wood flour becomes far less crystalline without undergoing solubilization. When 40% of the lignin was removed, the cellulose crystallinity index dropped below 45, resulting in >90% of the cellulose in wood flour to be hydrolyzed by Trichoderma viride cellulase. Emim CH₃COO was easily reused, thereby resulting in a highly concentrated solution of chemically unmodified lignin, which may serve as a valuable source of a polyaromatic material as a value-added product. Biotechnol. Bioeng. 2009;102: 1368-1376.
Historically, mulberry has been effectively used as a traditional medicine in Asia for the treatment of various infectious and internal diseases. It is a rich source of bioactive compounds that can ...promote human health. However, to date, it has not been officially or scientifically recognized because of a lack of accepted and standardized methodology for its evaluation. Numerous studies have been conducted by applying modern biotechnological tools to explore the relationship between the active ingredients in mulberry and their biological activities to solve ambiguities in their mechanism of action, opening a new horizon in traditional Chinese medicine with the potential for modernization in the near future.
This paper presents a concise overview on mulberry by examining its major bioactive components, including anthocyanins, polysaccharides, phenols, alkaloids and flavonoids. Recent technical advances are discussed for extraction (solid-liquid extraction, pressurized liquid extraction, supercritical-fluid extraction, microwave-assisted extraction, ultrasonic assisted extraction, enzymatic assisted extraction, solid-phase extraction) and separation (macroporous resins adsorption, silica gel chromatography, ion exchange chromatography, gel filtration chromatography, preparative liquid chromatography, countercurrent chromatography).
The mystery behind mulberry lies in various bioactivities that have been explored by modern technologies. Studies employing efficient, systematic, and practical protocols for sample preparation and isolation integrated with various analytical systems have been applied to discover, separate, and identify analytes in natural plants especially traditional Chinese medicines and to explore the scientific principles that will benefit the standardization and modernization of natural product research.
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•Mulberry is an excellent natural matrix due to its various and significant bioactive potential.•Hidden knowledge about mulberry is valuable to study and apply in functional foods and medicines.•Structure and bioactivities of main ingredients from mulberry are described.•Multidisciplinary approaches have been summarized to explore the mystery behind mulberry.•Reference for the modernization of natural product research is provided.
Neurodegenerative diseases are among the most widespread diseases affecting humans, and the number of patients is only rising. Seaweed polysaccharide extracts show significant neuroprotective and ...reparative activities. Seaweed polysaccharides might provide the next big breakthrough in neurodegenerative disease treatment. This paper reviews the applications of seaweed polysaccharides as potential treatments of neurodegenerative diseases. The particular focus is on fucoidan, ulvan, and their derivatives as potential agents to treat Alzheimer's disease. This review provides a critical update on the progress in this important research area.
Malonyl-CoA is the building block for fatty acid biosynthesis and also a precursor to various pharmaceutically and industrially valuable molecules, such as polyketides and biopolymers. However, ...intracellular malonyl-CoA is usually maintained at low levels, which poses great challenges to efficient microbial production of malonyl-CoA derived molecules. Inactivation of the malonyl-CoA consumption pathway to increase its intracellular availability is not applicable, since it is usually lethal to microorganisms. In this work, we employ synthetic antisense RNAs (asRNAs) to conditionally down-regulate fatty acid biosynthesis and achieve malonyl-CoA enrichment in Escherichia coli. The optimized asRNA constructs with a loop-stem structure exhibit high interference efficiency up to 80%, leading to a 4.5-fold increase in intracellular malonyl-CoA concentration when fabD gene expression is inhibited. Strikingly, this strategy allows the improved production of natural products 4-hydroxycoumarin, resveratrol, and naringenin by 2.53-, 1.70-, and 1.53-fold in E. coli, respectively. In addition, down-regulation of other fab genes including fabH, fabB, and fabF also leads to remarkable increases in 4-hydroxycoumarin production. This study demonstrates a novel strategy to enhance intracellular malonyl-CoA and indicates the effectiveness of asRNA as a powerful tool for use in metabolic engineering.
•Development of antisense RNA tools with high interference efficiency up to 80%.•Conditional down-regulation of fatty acid biosynthesis.•4.5-fold increase in intracellular malonyl-CoA concentration.•Application of the asRNA tool in improvement of natural products production.•A versatile strategy for manipulating essential genes in metabolic engineering.
Rhamnogalacturonan-I (RG-I)-enriched pectin (WRP) was recovered from citrus processing water by sequential acid and alkaline treatments in a previous study. RG-I-enriched pectin was proposed as a ...potential supplement for functional food and pharmaceutical development. However, previous studies illustrated that favorable modulations of gut microbiota by RG-I-enriched pectin were based on in vitro changes in the overall microbial structure and the question of whether there is a structure-dependent modulation of gut microbiota remains largely enigmatic. In the present study, modulations of gut microbiota by commercial pectin (CP), WRP and its depolymerized fraction (DWRP) with different RG-I contents and Mw were compared in vivo. It was revealed by 16s rRNA high-throughput sequencing that WRP and DWRP mainly composed of RG-I modulated the gut microbiota in a positive way. DWRP significantly increased the abundance of prebiotic such as Bifidobacterium spp., Lactobacillus spp., while WRP increased SCFAs producers including species in Ruminococcaceae family. By maintaining a more balanced gut microbiota composition and enriching some SCFA producers, dietary WRP and DWRP also elevated the SCFA content in the colon. Collectively, our findings offer new insights into the structure-activity correlation of citrus pectin and provide impetus towards the development of RG-I-enriched pectin with small molecular weight for specific use in health-promoting prebiotic ingredients and therapeutic products.
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