Glycosaminoglycan synthases

Sugar Polymer Engineering with Glycosaminoglycan Synthase Enzymes 5 to 5,000 Sugars and a Dozen Flavors... 

DeAngelis 50) transferred the glycosaminoglycan (GAG) synthase genes into Bacillus subtilis to produce GAG polymers. Well-defined GAG oligosaccharides were also produced using engineered variants of these enzymes. 

As stated above, hyaluronic acid (Figure 1.1), also called hyaluronan and sometimes presented as a hyaluronate (poly)anion from the chemical/structural viewpoint, is a non-sulfated GAG, while all other glycosaminoglycans are sulfated polysaccharides (cf. Table 1.1). Another fundamental and remarkable difference between HA and the other GAGs is the mean molar mass of the native biopolymeric chains. While the value of several MDa is the most common one for HA synthesized by hyaluronan synthases (HASl, HAS2, and HASS), the molar mass of further glycosaminoglycans, on average, does not exceed the value of 50 kDa [8]. 

It is believed that HA is the earliest evolutional form of glycosaminoglycans. Contrary to HA, other glycosaminoglycans are synthesized in the Golgi apparatus. They covalently bond with proteins to form the proteoglycans, which further transfer into the extracellular matrix by the exocytosis mechanism [41]. Three forms of hyaluronan synthase (HASj, HAS, HAS3) are found in human and vertebrate bodies. The enzyme HAS performs slow synthesis of high molecular weight HA, the enzyme... 

Contrary to sulfated glycosaminoglycans, synthesis of hyaluronan does not require active synthesis of the protein. Pre-existing hyaluronan synthases as transmembrane proteins contain cytoplasmic domain in which several sites - targets for phosphorylation by protein-kinases C and A - exist. The compounds, which increase the activity of the protein-kinase C (e.g. phorbol esters) and protein-kinase A, also accelerate the... 

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