Bacterial glycosyltransferase-mediated cell-surface chemoenzymatic glycan modification

Senlian Hong, Yujie Shi, Nicholas C. Wu, Geramie Grande, Lacey Douthit, Hua Wang, Wen Zhou, K. Barry Sharpless, Ian A. Wilson, Jia Xie () and Peng Wu ()
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Senlian Hong: The Scripps Research Institute
Yujie Shi: The Scripps Research Institute
Nicholas C. Wu: The Scripps Research Institute
Geramie Grande: The Scripps Research Institute
Lacey Douthit: The Scripps Research Institute
Hua Wang: The Scripps Research Institute
Wen Zhou: Peking University
K. Barry Sharpless: The Scripps Research Institute
Ian A. Wilson: The Scripps Research Institute
Jia Xie: The Scripps Research Institute
Peng Wu: The Scripps Research Institute

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Chemoenzymatic modification of cell-surface glycan structures has emerged as a complementary approach to metabolic oligosaccharide engineering. Here, we identify Pasteurella multocida α2-3-sialyltransferase M144D mutant, Photobacterium damsela α2-6-sialyltransferase, and Helicobacter mustelae α1-2-fucosyltransferase, as efficient tools for live-cell glycan modification. Combining these enzymes with Helicobacter pylori α1-3-fucosyltransferase, we develop a host-cell-based assay to probe glycan-mediated influenza A virus (IAV) infection including wild-type and mutant strains of H1N1 and H3N2 subtypes. At high NeuAcα2-6-Gal levels, the IAV-induced host-cell death is positively correlated with haemagglutinin (HA) binding affinity to NeuAcα2-6-Gal. Remarkably, an increment of host-cell-surface sialyl Lewis X (sLeX) exacerbates the killing by several wild-type IAV strains and a previously engineered mutant HK68-MTA. Structural alignment of HAs from HK68 and HK68-MTA suggests formation of a putative hydrogen bond between Trp222 of HA-HK68-MTA and the C-4 hydroxyl group of the α1-3-linked fucose of sLeX, which may account for the enhanced host cell killing of that mutant.

Date: 2019
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DOI: 10.1038/s41467-019-09608-w

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