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The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis

Author

Listed:
  • Kyle Rice

    (Wilfrid Laurier University)

  • Kissa Batul

    (Wilfrid Laurier University)

  • Jacqueline Whiteside

    (Wilfrid Laurier University)

  • Jayne Kelso

    (Wilfrid Laurier University)

  • Monica Papinski

    (Wilfrid Laurier University
    Wilfrid Laurier University)

  • Edward Schmidt

    (Wilfrid Laurier University)

  • Alena Pratasouskaya

    (Wilfrid Laurier University)

  • Dacheng Wang

    (Wilfrid Laurier University)

  • Rebecca Sullivan

    (Wilfrid Laurier University)

  • Christopher Bartlett

    (Wilfrid Laurier University)

  • Joel T. Weadge

    (Wilfrid Laurier University)

  • Marc W. Kamp

    (University of Bristol)

  • Gabriel Moreno-Hagelsieb

    (Wilfrid Laurier University)

  • Michael D. Suits

    (Wilfrid Laurier University)

  • Geoff P. Horsman

    (Wilfrid Laurier University)

Abstract

Phosphonates are rare and unusually bioactive natural products. However, most bacterial phosphonate biosynthetic capacity is dedicated to tailoring cell surfaces with molecules like 2-aminoethylphosphonate (AEP). Although phosphoenolpyruvate mutase (Ppm)-catalyzed installation of C-P bonds is known, subsequent phosphonyl tailoring (Pnt) pathway steps remain enigmatic. Here we identify nucleotidyltransferases in over two-thirds of phosphonate biosynthetic gene clusters, including direct fusions to ~60% of Ppm enzymes. We characterize two putative phosphonyl tailoring cytidylyltransferases (PntCs) that prefer AEP over phosphocholine (P-Cho) – a similar substrate used by the related enzyme LicC, which is a virulence factor in Streptococcus pneumoniae. PntC structural analyses reveal steric discrimination against phosphocholine. These findings highlight nucleotidyl activation as a predominant chemical logic in phosphonate biosynthesis and set the stage for probing diverse phosphonyl tailoring pathways.

Suggested Citation

  • Kyle Rice & Kissa Batul & Jacqueline Whiteside & Jayne Kelso & Monica Papinski & Edward Schmidt & Alena Pratasouskaya & Dacheng Wang & Rebecca Sullivan & Christopher Bartlett & Joel T. Weadge & Marc W, 2019. "The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11627-6
    DOI: 10.1038/s41467-019-11627-6
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    Cited by:

    1. Leixia Chu & Xiaoxia Luo & Taoting Zhu & Yingying Cao & Lili Zhang & Zixin Deng & Jiangtao Gao, 2022. "Harnessing phosphonate antibiotics argolaphos biosynthesis enables a synthetic biology-based green synthesis of glyphosate," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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