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Identification of D-arabinan-degrading enzymes in mycobacteria.

Omar Al-JouraniSamuel T BenedictJennifer RossAbigail J LaytonPhillip van der PeetVictoria M MarandoNicholas P BaileyTiaan HeunisJoseph ManionFrancesca MensitieriAaron FranklinJavier Abellon-RuizSophia L OramLauren ParsonsAlan CartmellGareth S A WrightArnaud BasléMatthias TrostBernard HenrissatJosé Luis Munoz-MunozRobert P HirtLaura L KiesslingAndrew Lee LoveringSpencer J WilliamsElisabeth C LowePatrick Joseph Moynihan
Published in: Nature communications (2023)
Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, we identify enzymes that cleave the D-arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria. We screened 14 human gut-derived Bacteroidetes for arabinogalactan-degrading activities and identified four families of glycoside hydrolases with activity against the D-arabinan or D-galactan components of arabinogalactan. Using one of these isolates with exo-D-galactofuranosidase activity, we generated enriched D-arabinan and used it to identify a strain of Dysgonomonas gadei as a D-arabinan degrader. This enabled the discovery of endo- and exo-acting enzymes that cleave D-arabinan, including members of the DUF2961 family (GH172) and a family of glycoside hydrolases (DUF4185/GH183) that display endo-D-arabinofuranase activity and are conserved in mycobacteria and other microbes. Mycobacterial genomes encode two conserved endo-D-arabinanases with different preferences for the D-arabinan-containing cell wall components arabinogalactan and lipoarabinomannan, suggesting they are important for cell wall modification and/or degradation. The discovery of these enzymes will support future studies into the structure and function of the mycobacterial cell wall.
Keyphrases
  • cell wall
  • mycobacterium tuberculosis
  • small molecule
  • transcription factor
  • endothelial cells
  • high throughput
  • pluripotent stem cells