Characterization of PmHS2 glycosyltransferases for the controlled synthesis of heparosan : a precursor of heparin and heparan sulfate

 Heparin (Hep), a highly sulfated and complex glycosaminoglycan polysaccharides, is worldwide used as an anticoagulant compound to prevent blood clotting during surgery. Heparin and its analogue, heparan sulfate (HS), have a large potential for medical applications. Nevertheless, the utilization of Hep/HS-based drugs in new therapeutic settings requires the synthesis of well-defined heparin and heparan sulfate-like molecules. Since neither the extraction from animal derivatives, nor the chemical synthesis, are suitable for the production of a large variety of defined Hep/HS polymers, there is a general interest in developing alternative systems enabling to tightly control Hep/HS synthesis. During the synthesis of heparin and heparan sulfate, the polymerization of the polysaccharide backbone, known as heparosan, determines the chain length and the size distribution of these polymers. Here, the Pasteurella multocida heparosan synthase PmHS2, a bacterial enzyme catalyzing the formation of heparosan polymers, was studied in detail in order to develop methods to control the polymer elongation.