Industrial production of glycosaminoglycans

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Datta, Payel
Linhardt, Robert J.
Sharfstein, Susan T.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Glycosaminoglycans (GAGs) are naturally occurring polysaccharides, composed of alternating sugar units; these include an amino sugar (e.g., N-acetyl glucosamine, GlcNAc or N-acetyl galactosamine, GalNAc) and either a galactose (Gal) or an uronic acid (GlcA or IdoA) (Fig. 1). The carbon backbone of the GAG chain may undergo no further modifications (e.g., hyaluronan) or may be further modified through sulfation, de-acetylation, and/or epimerization (e.g., heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate and keratan sulfate). Simple non-sulfated GAGs (e.g., hyaluronan) and the precursors of highly sulfated GAGs (e.g., heparosan and chondroitin) are produced in certain bacteria as well as in animals (Cress et al., 2014) These simple GAGs are thought to contribute to pathogenicity of the host bacteria. Simple, non-sulfated GAGs as well as the highly modified sulfated GAGs (e.g., heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate and keratan sulfate) are produced in all animals, including humans. In humans, hyaluronan is part of the connective tissue extracellular matrix (ECM) and is involved in biological functions such as lubrication of joints. Highly sulfated GAGs have tissue-specific sulfated domains that are binding sites for various proteins (Capila and Linhardt, 2002) and, therefore, play critical roles in biological functions such as homeostasis, cell growth, cell migration, development, morphogenesis, tissue repair, and angiogenesis (Linhardt and Toida, 2004; Linhardt, 2003). The current industrial production of GAGs can be broadly classified into three categories: (1) industrial production from animal source, (2) industrial production using microbial cells, and (3) industrial production using eukaryotes. Various GAGs have been routinely extracted and purified from animal sources, for example, hyaluronan from rooster combs, and heparin from pig intestines or bovine lung. An increased knowledge of GAG biosynthesis, as well as the advances in metabolic engineering strategies, bioprocess optimization, downstream processing approaches and analytical tools have led to the production of GAGs from microbial cells and exploration of eukaryotic cells, for example, CHO cells, toward heparin production.
Reference Module in Life Sciences 2017, 1-10
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Industrial production of glycosaminoglycans, P. Datta, R. J. Linhardt, S. T. Sharfstein, Reference Module in Life Sciences 2017, 1-10, 2018.
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