Synthesis, structural elucidation, and biochemical analysis of immunoactive glucuronosyl diacylglycerides of mycobacteria and corynebacteria

J Org Chem. 2013 Mar 15;78(6):2175-90. doi: 10.1021/jo302508e. Epub 2013 Jan 30.

Abstract

Glucuronosyl diacylglycerides (GlcAGroAc2) are functionally important glycolipids and membrane anchors for cell wall lipoglycans in the Corynebacteria. Here we describe the complete synthesis of distinct acyl-isoforms of GlcAGroAc2 bearing both acylation patterns of (R)-tuberculostearic acid (C19:0) and palmitic acid (C16:0) and their mass spectral characterization. Collision-induced fragmentation mass spectrometry identified characteristic fragment ions that were used to develop "rules" allowing the assignment of the acylation pattern as C19:0 (sn-1), C16:0 (sn-2) in the natural product from Mycobacterium smegmatis, and the structural assignment of related C18:1 (sn-1), C16:0 (sn-2) GlcAGroAc2 glycolipids from M. smegmatis and Corynebacterium glutamicum. A synthetic hydrophobic octyl glucuronoside was used to characterize the GDP-mannose-dependent mannosyltransferase MgtA from C. glutamicum that extends GlcAGroAc2. This enzyme is an Mg(2+)/Mn(2+)-dependent metalloenzyme that undergoes dramatic activation upon reduction with dithiothreitol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Biosynthetic Pathways
  • Corynebacterium / chemistry*
  • Glycerides / analysis*
  • Glycerides / chemical synthesis*
  • Glycerides / chemistry
  • Glycolipids / analysis*
  • Glycolipids / chemical synthesis*
  • Glycolipids / chemistry
  • Magnesium / chemistry*
  • Mannosyltransferases / chemistry*
  • Mass Spectrometry
  • Mycobacterium / chemistry*
  • Mycobacterium smegmatis / chemistry*
  • Stearic Acids / chemistry*

Substances

  • Bacterial Proteins
  • Glycerides
  • Glycolipids
  • Stearic Acids
  • tuberculostearic acid
  • GDP-mannosyltransferase
  • Mannosyltransferases
  • Magnesium