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Biosynthetic polysaccharide-based drugs and nutraceuticals from non-animal sources

Glycosaminoglycans (GAGs) are a class of naturally occurring polysaccharides that play vital roles in cellular functions. GAGs (eg, hyaluronic acid, heparosan, chondroitin, chondroitin sulfate, heparan sulfate and heparin) have also been utilised in biopharmaceutical and nutraceutical industries. Animal-sourced GAGs can contain process impurities and contaminants, which may result in adverse effects. To overcome this issue, efforts have focused on the industrial production of animal-component free GAGs. This review focuses on the production of tailored biosynthetic GAGs that have specific and novel functions, including biosynthetic heparins, potential anti-viral and drug delivery applications.

Biosynthetic pathways

Introduction

GAGs are a family of linear polysaccharides containing repeating disaccharide units of uronic acid and N-acetyl glucosamine (GlcNAc) or N-acetyl galactosamine (GalNAc). Non-sulfated GAGs (eg, hyaluronic acid, heparosan and chondroitin) are biosynthesised in certain prokaryotes. These non-sulfated GAGs are bacterial capsular polysaccharides (CPS) and contribute to the pathogenicity and survival of these bacteria in their host. These non-sulfated GAGs are also produced in animal cells and, in some cases, are the precursor backbones for sulfated GAGs (eg, heparin, heparan sulfate, chondroitin sulfate and dermatan sulfate). For example, heparosan is the non-sulfated linear polysaccharide composed of the repeating disaccharide unit [→4) β-D-glucuronic acid (GlcA) (1→4) α-D-(GlcNAc) (1→]n. The heparosan chain is sequentially modified by tissue-specific sulfotransferases and C5-epimerase to form sulfated heparan sulfate and highly sulfated heparin. Chondroitin, [→4)β-D-GlcA (1→3)α-D-GalNAc) (1→]n, is similarly transformed to chondroitin sulfate or dermatan sulfate. The sulfated domains within these sulfated GAGs serve as the binding sites for specific biological macromolecules, including blood proteins and viral capsular proteins. For instance, heparin is produced chiefly in the mast cells and comprised of highly sulfated pentasaccharide domains that bind to antithrombin III, preventing coagulation. Unfractionated heparins and low molecular weight heparins have been widely used as an anticoagulant drug.











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