Synthesis of N-Acetyllactosamine and N-Acetyllactosamine-Based Bioactives

Abstract

N-Acetyllactosamine (LacNAc), or more specifically β-D-galactopyranosyl-1,4-N-acetyl-Dglucosamine, is a unique acyl-amino sugar and a key structural unit in human milk oligosaccharides, an antigen component of many glycoproteins and an antiviral active component for the development of effective drugs against viruses. LacNAc is useful itself and as a basic building block for producing various bioactive oligosaccharides, notably because this synthesis may be used to add value to dairy lactose. Despite a significant amount of information in the literature on the benefits, structures and types of different LacNAc-derived oligosaccharides, knowledge about their effective synthesis for large scale production is still in its infancy. This work provides a comprehensive analysis of existing production strategies of LacNAc and important LacNAc-based structures, including sialylated LacNAc, as well as poly-and oligo-LacNAc. We conclude that direct extraction from milk is too complex, while chemical synthesis is also impractical at an industrial scale. Microbial routes have application when multiple step reactions are needed but the major route to large scale biochemical production will likely lie with enzymatic routes, particularly those using β-galactosidases (for LacNAc synthesis), sialidases (for sialylated LacNAc synthesis) and β-N-acetylhexosaminidases (for oligo-LacNAc synthesis).Glycosyltransferases, especially for the biosynthesis of extended complex LacNAc structures, could also play a major role in the future. In these cases, immobilization of the enzyme can increase stability and reduce cost. Processing parameters, such as substrate concentration and purity, acceptor to donor ratio, water activity and temperature can affect product selectivity and yield.More work is needed to optimize these reaction parameters and in the development of robust, thermally stable enzymes to facilitate commercial production of these important bioactive substances. Abbreviations: 39 β3GalT β1-3 galactosyltransferase β4GalT β1-4 galactosyltransferase CMP-NeuNAc cytidine-5'-monophosphate-5-N-acetylneuraminic acid DS'LNT α2-6-linked disialyllacto-N-tetraose DSLNnT α2-6-linked disialyllacto-N-neotetraose EPEC enteropathogenic Escherichia coli GalNAc N-acetylgalactosamine GfCoV Guinea fowl coronavirus GlcNAc N-acetylglucosamine GLP-1 glucagon-like peptide 1 HEp-2 human epithelial type 2 cells iGnT β1-3 N-acetylglucosaminyltransferase IGnT β1-6 N-acetylglucosaminyltransferase iLNO iso-Lacto-N-octaose LacNAc N-acetyllactosamine LacNAc-ITag imidazolium-tagged LacNAc LacY β-galactoside permease lacZ β-galactosidase gene lgtA β1-3 N-acetylglucosaminyltransferase gene lgtB β1-4 galactosyltransferase gene LND Lacto-N-decaose LNH Lacto-N-hexaose LNnD Lacto-N-neo-decaose LNnH Lacto-N-neo-hexaose LNnO Lacto-N-neo-octaose LNnT Lacto-N-neotetraose LNO Lacto-N-octaose LNT Lacto-N-tetraose ManNAc N-acetylmannosamine MERS-CoV Middle East respiratory syndrome coronavirus Neu5Ac N-acetylneuraminic acid oNPG ortho-nitrophenyl-β-galactoside pLNH para-Lacto-N...

Comparative putative metabolites profiling of Tachypleus gigas and Carcinoscorpius rotundicauda hemocytes stimulated with lipopolysaccharide

“…However, the Tukey test shows that the increment and reduction are not statistically significant. N-acetyllactosamine (LacNAc), specifically β-d-galactopyranosyl-1,4-N-acetyl-d-glucosamine, is a unique acyl-amino sugar and a critical structural unit in human milk oligosaccharides, an antigen component of many glycoproteins, and an active antiviral property for the development of effective drugs against viruses 49 . The 6-sulfo -N-acetyllactosamine was found to inhibit the binding of the SARS-CoV-2 spike protein S1 subunit with blood group A RBCs and reduce the interaction between the spike protein S1 subunit and Angiotensin-converting enzyme 2 (ACE2) in SARS-CoV-2 infection 50 .…”

Bioactives from Whey: A Sustainable Approach to Enzymatic Production of Sialyl-N-acetyllactosamine

“…Performing trans-sialylation at a higher temperature may modify the relative hydrolysis and trans-sialylation rates. , Thus, we further ran the enzymatic reaction at elevated temperatures up to 60 °C. As shown in Figure D, slightly higher concentrations of 3′-SLN can be obtained at 35 and 40 °C compared to those obtained at 30 °C after 60 min.…”

Comparative putative metabolites profiling of Tachypleus gigas and Carcinoscorpius rotundicauda hemocytes stimulated with lipopolysaccharide

“…However, the Tukey test shows that the increment and reduction are not statistically signi cant. N-acetyllactosamine (LacNAc), speci cally β-d-galactopyranosyl-1,4-N-acetyl-dglucosamine, is a unique acyl-amino sugar and a critical structural unit in human milk oligosaccharides, an antigen component of many glycoproteins, and an active antiviral property for the development of effective drugs against viruses [49]. The 6-sulfo -N-acetyllactosamine was found to inhibit the binding of the SARS-CoV-2 spike protein S1 subunit with blood group A RBCs and reduce the interaction between the spike protein S1 subunit and Angiotensin-converting enzyme 2 (ACE2) in SARS-CoV-2 infection [50].…”