A Novel Marine Bacterium-Derived Heparinase with High Potential for the Structure-Function Studies of Heparin/Heparan Sulfate

Abstract

Heparinases are crucial for deciphering heparin/heparan sulfate (HP/HS) structures; yet most known heparinases from terrestrial sources share similar properties. Here, we identify a novel heparinase, HD1492, from HP-cultured marine bacterial metagenomes. Although phylogenetically classified as heparinase II, its exhibits unique enzymatic properties by preferentially cleaving sulfated regions in HP/HS and generating resistant oligosaccharides from low-sulfated HS. These oligosaccharides have a signature feature: one or several nonsulfated disaccharides linked to an N-sulfated disaccharide at the reducing end. This property enables HD1492 to reveal the distribution and composition of nonsulfated domains in HP/HS─overcoming the limitation of conventional disaccharide analysis─as validated in mouse organ-derived GAGs and the drug sulodexide. Overall, the unique enzymatic properties of HD1492 confer innovative value that distinguishes it from terrestrial heparinases, providing a much-needed tool for the resolution of HP/HS structural and functional domains and the development and quality control of related products.

Keywords: heparan sulfate; heparin; heparinase; marine bacteria; substrate selectivity.