Synthesis of α-glucan in mycobacteria involves a hetero-octameric complex of trehalose synthase TreS and Maltokinase Pep2

ACS Chem Biol. 2013 Oct 18;8(10):2245-55. doi: 10.1021/cb400508k. Epub 2013 Aug 13.


Recent evidence established that the cell envelope of Mycobacterium tuberculosis, the bacillus causing tuberculosis (TB), is coated by an α-glucan-containing capsule that has been implicated in persistence in a mouse infection model. As one of three known metabolic routes to α-glucan in mycobacteria, the cytoplasmic GlgE-pathway converts trehalose to α(1 → 4),α(1 → 6)-linked glucan in 4 steps. Whether individual reaction steps, catalyzed by trehalose synthase TreS, maltokinase Pep2, and glycosyltransferases GlgE and GlgB, occur independently or in a coordinated fashion is not known. Here, we report the crystal structure of M. tuberculosis TreS, and show by small-angle X-ray scattering and analytical ultracentrifugation that TreS forms tetramers in solution. Together with Pep2, TreS forms a hetero-octameric complex, and we demonstrate that complex formation markedly accelerates maltokinase activity of Pep2. Thus, complex formation may act as part of a regulatory mechanism of the GlgE pathway, which overall must avoid accumulation of toxic pathway intermediates, such as maltose-1-phosphate, and optimize the use of scarce nutrients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalytic Domain
  • Coordination Complexes / metabolism*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Glucans / biosynthesis*
  • Glucans / metabolism
  • Glucosyltransferases / metabolism*
  • Mice
  • Models, Molecular
  • Mycobacterium tuberculosis / enzymology*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Signal Transduction


  • Coordination Complexes
  • Glucans
  • Glucosyltransferases
  • trehalose synthase
  • Phosphotransferases (Alcohol Group Acceptor)
  • maltokinase