2011 OSU Molecular Life Sciences
Interdisciplinary Graduate Programs Symposium

 

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Poster number 79 submitted by Katelyn Zak

In vivo production of fucose-α1, 2-lactose

Katelyn Zak (Biochemistry, OSU)

Abstract:
The third largest component of human milk is complex, minimally metabolized oligosaccharides that serve to protect the infant’s health both by promoting infant intestinal microbiota and warding away harmful pathogens. The mother’s blood type cause structural variations and change human milk oligosaccharide (HMO) concentrations during lactation. While HMOs can promote growth of infant intestinal microbiota, their best characterized function is their prebiotic effects. HMOs have anti-adhesive effects prohibiting pathogens from binding to intestinal epithelial cells as well as modifying surface glycans that pathogens use to facilitate their entry. Fucosylated oligosaccharides comprise eighty percent of all HMOs of which 2-linked fucosyloligosaccharides appear the most biologically significant. The current hurdle in HMO research is the lack of large scale synthesis of HMOs to further test their biological significance. From clinical trials, fucose-α1, 2-lactose protects against diarrhea significantly better than non-2-linked fucosyloligosaccharides. Fucose-α1, 2-lactose may be produced in large scale quantities by recombinant E. coli which utilize enzymes FKP (fucokinase pyrophosphorylase) and WbsJ (α1, 2-fucoslytransferase) to enzymatically synthesize fucose-α1, 2-lactose. FKP is a bifunctional enzyme which catalyzes the reaction between fucose, ATP, and GTP to produce the expensive and hard to obtain GDP-fucose, meanwhile WbsJ is a known α1, 2-FucT which demonstrates promiscuous acceptor substrate specificity. This method is cost effective by regenerating the sugar nucleotides required for the synthesis and require only inexpensive, commercially available, fucose and lactose.

Keywords: Human milk oligosaccharides, Fucose-1, 2-lactose