Chemoenzymatic synthesis of polyprenyl phosphates

Bioorg Med Chem. 2008 May 1;16(9):5149-56. doi: 10.1016/j.bmc.2008.03.025. Epub 2008 Mar 14.

Abstract

Polyprenyl phosphates, including undecaprenyl phosphate and dolichyl phosphate, are essential intermediates in several important biochemical pathways including N-linked protein glycosylation in eukaryotes and prokaryotes and prokaryotic cell wall biosynthesis. Herein, we describe the evaluation of three potential undecaprenol kinases as agents for the chemoenzymatic synthesis of polyprenyl phosphates. Target enzymes were expressed in crude cell envelope fractions and quantified via the use of luminescent lanthanide-binding tags (LBTs). The Streptococcus mutans diacylglycerol kinase (DGK) was shown to be a very useful agent for polyprenol phosphorylation using ATP as the phosphoryl transfer agent. In addition, the S. mutans DGK can be coupled with two Campylobacter jejuni glycosyltransferases involved in N-linked glycosylation to efficiently biosynthesize the undecaprenyl pyrophosphate-linked disaccharide needed for studies of PglB, the C. jejuni oligosaccharyl transferase.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Campylobacter jejuni / enzymology
  • Campylobacter jejuni / genetics
  • Cloning, Molecular
  • Diacylglycerol Kinase / chemistry*
  • Diacylglycerol Kinase / genetics
  • Diacylglycerol Kinase / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Glycosylation
  • Glycosyltransferases / chemistry*
  • Glycosyltransferases / genetics
  • Glycosyltransferases / metabolism
  • Luminescence
  • Molecular Structure
  • Phosphorylation
  • Polyisoprenyl Phosphates / chemical synthesis*
  • Polyisoprenyl Phosphates / chemistry
  • Stereoisomerism
  • Streptococcus mutans / enzymology
  • Streptococcus mutans / genetics
  • Time Factors

Substances

  • Polyisoprenyl Phosphates
  • Glycosyltransferases
  • Diacylglycerol Kinase