Enzymatic Synthesis of Heparin - Sustainable Biotechnology: Sources of Renewable Energy - page 259

Enzymatic Synthesis of Heparin

Renpeng Liu and Jian Liu

Abstract Heparin and low-molecular-weight heparin have been used as antico-
agulant drugs for decades. Pharmaceutical grade heparin is derived from mucosal
tissues of slaughtered domestic animals. However, heparin can have severe side
effects, has a potential risk of contamination and unstable resources. Thus, synthetic
heparin that can be manufactured in a controlled environment is desirable. Although
traditional chemical synthesis has successfully reduced the structural complexity of
heparin, chemical synthesis of the heparin oligosaccharide is tedious and costly.
In this review, we summarize recent progress toward the enzymatic synthesis of
heparin/heparan sulfate. We will emphasize the efforts to develop novel enzymatic
approaches for the synthesis of heparan sulfate mimics from Escherichia coli hep-
arosan and to produce polysaccharide and oligosaccharide end products with high
specificity for the biological target. These advancements provide the foundation for
the development of heparan sulfate/heparin-based therapeutic agents.

Keywords Anticoagulant · Enzymatic synthesis · Heparan sulfate · Heparin

1 Introduction

Heparan sulfate (HS) is a highly sulfated polysaccharide that represents a unique
class of natural products. Heparin is a special type of HS synthesized within mast
cells. It was discovered in 1918 [1] and has been widely used as an anticoagu-
lant drug for decades. HS/heparin consists of 50-100 disaccharide units carrying
sulfo- groups. Pharmaceutical grade heparin is derived from slaughtered domestic
animal mucosal tissues such as porcine intestine or bovine lung. Its complex struc-
ture causes many of the unwanted side effects of heparin, including hemorrhage, and