Enzymatic Synthesis of Heparin - Sustainable Biotechnology: Sources of Renewable Energy - page 274

our understanding of HS biosynthesis. Most importantly, these efforts not only allow
us to investigate novel synthesis of anticoagulant heparin, but also lead to a general
method for preparation of structurally defined HS with various biological functions
and to help develop novel heparin/HS based therapeutic agents.
5 Expert Commentary and 5 Year View
Heparin is a commonly used anticoagulant drug with annual sales close to $4 bil-
lion worldwide. Drawbacks of the drug include vulnerable supply of raw materials,
severe side effects, and potential risk of contaminants [13, 60]. Over the past decade,
many groups have achieved considerable progress in understanding heparin/HS
biosynthesis, especially in the efforts to develop novel enzymatic approaches to
synthesize HS from heparosan and to produce polysaccharide and oligosaccharide
end products with high specificity for the biological targets [60]. It should be noted
that heparosan can be prepared in a pharmaceutical manufacturing environment.
Thus, synthetic heparin will eliminate the possibility of contamination and give the
drug manufacturer a complete control over the safety and purity of the product.
Optimizing the synthetic procedure will allow us to produce heparin with maximum
pharmacological effects. The enzymatic synthesis will also provide an alternative
approach to prepare structurally defined oligosaccharides. Although the synthesis
of each different type of heparin/HS oligosaccharide remains a daunting task, the
recent investigations reviewed above may accelerate our understanding of enzy-
matic/chemoenzymatic synthesis and help the future development of heparin/HS
based drug from non-animal natural sources. Future direction includes the substrate
specificity of biosynthetic enzymes, synthesis of structurally defined HS backbone,
and utility of unnatural UDP-sugar donors as well as the molecular mechanism
controlling the mode of heparin/HS action.
Acknowledgements Our research is supported in part by grants from National Institute of Health
(AI050050) and from American Heart Association, MidAtlantic (0855424E).
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