S24: Chemoenzymatic synthesis of bioengineered heparin

Glycosaminoglycans (GAGs) are anionic polysaccharides of critical importance in human biology. Heparin, the most highly sulfated GAG has been used as an anticoagulant for over 75 years. Currently heparin and related low molecular weight heparins are prepared by extraction from porcine tissue.  We have developed an efficient chemoenzymatic synthesis of heparin from a non-animal source.  The varying sulfo group patterns make heparin chain an extremely challenging target.  Here, we show our efforts to synthesize heparin for E. coli K5 capsular polysaccharide using a chemoenzymatic approach relying on biosynthetic enzymes, including sulfotransferases and epimerase.  Chemoenzymatic synthesis is reliable over a wide range of scales and should be useful in both research and pharmaceutical applications.