A beta-1,4-galactosyltransferase from Helicobacter pylori is an efficient and versatile biocatalyst displaying a novel activity for thioglycoside synthesis.

Helicobacter pylori is a highly persistent and common pathogen in humans. It is the causative agent of chronic gastritis and its further stages. HP0826 is the beta-1,4-galactosyltransferase involved in the biosynthesis of the LPS O-chain backbone of H. pylori. Though it was first cloned nearly a decade ago, there are surprisingly limited data about the characteristics of HP0826, especially given its prominent role in H. pylori pathogenicity. We here demonstrate that HP0826 is a highly efficient and promiscuous biocatalyst. We have exploited two novel enzymatic activities for the quantitative synthesis of the thiodisaccharide Gal-beta-S-1,4-GlcNAc-pNP as well as Gal-beta-1,4-Man-pNP. We further show that Neisseria meningitidis beta-1,4-galactosyltransferases LgtB can be used as an equally efficient catalyst in the latter reaction. Thiodisaccharides have been extensively used in structural biology but can also have therapeutic uses. The Gal-beta-1,4-Man linkage is found in the Leishmania species LPG backbone disaccharide repeats and cap, which have been associated with vector binding in Leishmaniasis.