Enzymatic Building‐Block Synthesis for Solid‐Phase Automated Glycan Assembly

• Published in: Angewandte Chemie International Edition 2020-12, Vol.59 (50), p.22456-22459
• Main Authors: Marchesi, Andrea, Parmeggiani, Fabio, Louçano, João, Mattey, Ashley P., Huang, Kun, Gupta, Tanistha, Salwiczek, Mario, Flitsch, Sabine L.
• Format: Article
• Language: English
• Subjects: Assembly; Automation; biocatalysis; Carbohydrate Conformation; Catalysis; Cell surface; Chemical synthesis; chemoenzymatic synthesis; Communication; Communications; Galactosyltransferases - metabolism; Glycan; glycans; Lactose; Neisseria meningitidis - enzymology; Oligosaccharides; Polysaccharides; Polysaccharides - biosynthesis; Polysaccharides - chemistry; Reagents; Sucrose; Sugar; transgalactosylation
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202008067

Automated chemical oligosaccharide synthesis is an attractive concept that has been successfully applied to a large number of target structures, but requires excess quantities of suitably protected and activated building blocks. Herein we demonstrate the use of biocatalysis to supply such reagents for automated synthesis. By using the promiscuous NmLgtB‐B β1‐4 galactosyltransferase from Neisseria meningitidis we demonstrate fast and robust access to the LacNAc motif, common to many cell‐surface glycans, starting from either lactose or sucrose as glycosyl donors. The enzymatic product was shown to be successfully incorporated as a complete unit into a tetrasaccharide target by automated assembly. In a chemoenzymatic approach to oligosaccharide synthesis, the scalability potential of enzymatic synthesis was exploited for the preparative synthesis of a relevant N‐acetyllactosamine disaccharide building block. This disaccharide was then applied successfully to the automated synthesis of a target oligosaccharide using the glycan synthesizer Glyconeer 2.1 (see scheme).