Enzyme and microbial technology for synthesis of bioactive oligosaccharides: an update
Oligosaccharides, in either free or bound forms, play crucial roles in a wide range of biological processes. Increasing appreciation of their roles in cellular communication, interaction, pathogenesis, and prebiotic functions has stimulated tremendous interests in their synthesis. Pure and structurally defined oligosaccharides are essential for fundamental studies. On the other hand, for those with near term medical and nutraceutical applications, their large-scale synthesis is necessary. Unfortunately, oligosaccharides are notoriously difficult in their synthesis, and their enormous diverse structures leave a vast gap between what have been synthesized in laboratory and those present in various biological systems. While enzymes and microbes are nature’s catalysts for oligosaccharides, their effective use is not without challenges. Using examples of galactose-containing oligosaccharides, this review analyzes the pros and cons of these two forms of biocatalysts and provides an updated view on the status of biocatalysis in this important field. Over the past few years, a large number of novel galactosidases were discovered and/or engineered for improved synthesis via transglycosylation. The use of salvage pathway for regeneration of uridine diphosphate (UDP)-galactose has made the use of Leloir glycosyltransferases simpler and more efficient. The recent success of large-scale synthesis of 2′ fucosyllactose heralded the power of whole-cell biocatalysis as a scalable technology. While it still lags behind enzyme catalysis in terms of the number of oligosaccharides synthesized, an acceleration in the use of this form of biocatalyst is expected as rapid advances in synthetic biology have made the engineering of whole cell biocatalysts less arduous and less time consuming.
KeywordsOligosaccharide synthesis Glycosyltransferase Sugar nucleotides Whole-cell biocatalysis Enzymatic synthesis Galactosidase
Research on complex carbohydrate synthesis in Chen Laboratory at Georgia Institute of Technology is supported by grants from US National Science Foundation, BES-0455193 and CBET-1509202.
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Conflict of interest
The author declares that she has no conflict of interest.
- Koizumi S, Endo T, Tabata K and Ozaki A (1998) Large-scale production of UDP-galactose and globotriose by coupling metabolically engineered bacteria. Nature Biotechnol 16:847–850Google Scholar
- Shao J, Hayashi T, wang PG (2003) Enhanced production of alpha-galactosyl epitopes by metabolically engineered Pichia pastoris. Appl Environ Microbiol 69(9):5238–5242Google Scholar
- Usvalampi A, Maaheimo H, Tossavainen O, Frey AD (2017) Enzymatic synthesis of fucose-containing galacto-oligosaccharides using β-galactosidase and identification of novel disaccharide structures. Glycoconj J. https://doi.org/10.1007/s10719-017-9794-3
- Vasta GR (2009) Roles of glactins in infection. Nat Rev Microbiol 7:424–38Google Scholar
- Wang S, Czuchry D, Liu B, Vinnikova AN, Gao Y, Vlahakis JZ, Szarek WA, Wang L, Feng L, Brockhausen I (2014) Characterization of two UDP-Gal: GalNAc-diphosphate-lipid b1,3-galacosyltransferases WbwcC from Escherichia coli serotypes O104 and O5. J Bacteriol 196(17):3122–3133CrossRefPubMedPubMedCentralGoogle Scholar
- Xu C, Liu B, Hu B, Han Y, Feng L, Allingham JS, Szarek WA, Wang L, Brockhausen I (2011) Biochemical characterization of UDP-Gal: GlcNAc-pyrophosphate-lipid b1,4 galactosyltransferase WfeD, a new enzyme from Shigella boydii type 14 that catalyzes the second step in O-antigen repeating-unit synthesis. J Bacteriol 193(2):449–459CrossRefPubMedGoogle Scholar