Functional expression of L-fucokinase/guanosine 5'-diphosphate-L-fucose pyrophosphorylase from Bacteroides fragilis in Saccharomyces cerevisiae for the production of nucleotide sugars from exogenous monosaccharides

Glycobiology. 2011 Sep;21(9):1228-36. doi: 10.1093/glycob/cwr057. Epub 2011 Apr 22.

Abstract

The biosynthesis of glycoconjugates requires the relevant glycosyltransferases and nucleotide sugars that can act as donors. Given the biological importance of posttranslational glycosylation, a facile, robust and cost-effective strategy for the synthesis of nucleotide sugars is highly desirable. In this study, we demonstrate the synthesis of nucleotide sugars from corresponding monosaccharides in a highly efficient manner via metabolic engineering, using an enzymatic approach. This method exploits l-fucokinase/guanosine 5'-diphosphate (GDP)-l-fucose (L-Fuc) pyrophosphorylase (FKP), a bifunctional enzyme isolated from Bacteroides fragilis 9343, which converts l-Fuc into GDP-L-Fuc via an L-Fuc-1-phosphate intermediate. Because L-Fuc and d-arabinose (D-Ara) are structurally similar, it is assumed that the biosynthesis of GDP-D-Ara in a recombinant Saccharomyces cerevisiae strain harboring the FKP gene can occur through a mechanism akin to that of GDP-L-Fuc via the salvage pathway. Thus, we reasoned that by exogenously supplying different monosaccharides structurally related to L-Fuc, it should be possible to produce the corresponding nucleotide sugars with this recombinant yeast strain, regardless of internal acquisition of nucleotide sugars through expression of additive enzymes in the de novo pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteroides fragilis / chemistry
  • Bacteroides fragilis / enzymology*
  • Cloning, Molecular
  • Electrophoresis, Polyacrylamide Gel
  • Genetic Engineering / methods*
  • Glycoconjugates / biosynthesis*
  • Glycosylation
  • Guanosine Diphosphate Fucose / metabolism*
  • Kinetics
  • Monosaccharides / metabolism
  • Nucleotides / biosynthesis*
  • Organisms, Genetically Modified
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Plasmids
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Spectrometry, Mass, Electrospray Ionization
  • Transformation, Genetic

Substances

  • Glycoconjugates
  • Monosaccharides
  • Nucleotides
  • Recombinant Proteins
  • Guanosine Diphosphate Fucose
  • Phosphotransferases (Alcohol Group Acceptor)
  • fucokinase