Abstract
Hyaluronic acid, or HA, is a rigid and linear biopolymer belonging to the class of the glycosaminoglycans, and composed of repeating units of the monosaccharides glucuronic acid and N-acetylglucosamine. HA has multiple important functions in the human body, due to its properties such as bio-compatibility, lubricity and hydrophilicity, it is widely applied in the biomedical, food, health and cosmetic fields. The growing interest in this molecule has motivated the discovery of new ways of obtaining it. Traditionally, HA has been extracted from rooster comb-like animal tissues. However, due to legislation laws HA is now being produced by bacterial fermentation using Streptococcus zooepidemicus, a natural producer of HA, despite it being a pathogenic microorganism. With the expansion of new genetic engineering technologies, the use of organisms that are non-natural producers of HA has also made it possible to obtain such a polymer. Most of the published reviews have focused on HA formulation and its effects on different body tissues, whereas very few of them describe the microbial basis of HA production. Therefore, for the first time this review has compiled the molecular and genetic bases for natural HA production in microorganisms together with the main strategies employed for heterologous production of HA.
Highlights
Basis of HA synthesis: HA‐synthases The synthesis of a HA chain in all natural producers initially emerge from the glycolytic pathway
From the deviation of the glycolytic pathway to the production HA there is the production of molecules used by cells as wall polysaccharide synthesis, synthesis of teichoic acids and peptidoglycan (Fig. 3) which corresponds to 20 % of dry weight of a regular cell [25]
Once available in the cell, UDP-GlcUA and UDP-GlcNAc are used as substrates by hyaluronan synthase enzyme (HAS), an enzyme that have transmembrane domains and catalyze the union of the two sugar precursors intracellularly to release the chain in the extracellular matrix (Fig. 3) [30]
Summary
Hyaluronic acid, called hyaluronan or hyaluronate (HA), is considered an important glycosaminoglycans due to its varied physiological functions. HA reaches higher concentrations in the cartilage tissue in the vitreous humor [5], the synovial fluid of the joints [6] and in the umbilical cord [7] and is responsible for the maintenance of tissue homeostasis [8] This polymer is directly involved in processes such as embryogenesis [9], inflammation [10], metastasis or tumor progression phenomenon [11], angiogenesis [12] and the healing process [13]. Together with the increased number of applications of hyaluronic acid, the market share tends to grow over the years This polymer is valued at USD 1000– 5000/kg depending on its purity and size [22].
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