Hyaluronan is a polysaccharide with multiple functions in the human body being involved in creating flexible and protective layers in tissues and in many signalling pathways during embryonic development, wound healing, inflammation, and cancer. Hyaluronan is an important component of active pharmaceutical ingredients for treatment of, for example, arthritis and osteoarthritis, and its commercial value far exceeds that of other microbial extracellular polysaccharides. Traditionally hyaluronan is extracted from animal waste which is a well-established process now. However, biotechnological synthesis of biopolymers provides a wealth of new possibilities. Therefore, genetic/metabolic engineering has been applied in the area of tailor-made hyaluronan synthesis. Another approach is the controlled artificial (in vitro) synthesis of hyaluronan by enzymes. Advantage of using microbial and enzymatic synthesis for hyaluronan production is the simpler downstream processing and a reduced risk of viral contamination. In this paper an overview of the different methods used to produce hyaluronan is presented. Emphasis is on the advancements made in the field of the synthesis of bioengineered hyaluronan. 1. Introduction Hyaluronic acid, also known as hyaluronan, is a linear polysaccharide composed of a repeating disaccharide unit of β(1,4)-glucuronic acid (GlcUA)-β(1,3)-N-acetylglucosamine (GlcNAc) (Figure 1). Both individual carbohydrate residues in hyaluronan adopt the stable chair conformation which determines the conformation of the polymer in solution that is described as an overall random coil structure that may have also highly flexible regions. Nevertheless, in terms of chemical structure, hyaluronan is a simple linear polymer with high molecular mass and exceptional rheological properties. Hyaluronan is a member of the glycosaminoglycans family that includes chondroitin/dermatan sulfate, keratan sulfate, and heparin/heparan sulfate, each with a characteristic disaccharide-repeating structure of an amino sugar, either glucosamine or galactosamine, and a hexose, either galactose, glucuronic acid, or iduronic acid, which can be carboxylated or sulfated [1]. Hyaluronan is the only glycosaminoglycan member that is not sulfated and is not covalently bound to a proteoglycan core protein. Figure 1: Repeating unit of hyaluronan. Research on hyaluronan expands over more than one century (Table 1). The first report that can be linked to hyaluronan dates from 1880, when the French chemist Portes observed that the mucin in the vitreous body, which he named “hyalomucine,”
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