The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis

Kyle Rice, Kissa Batul, Jaqueline Whiteside, Jayne Kelso, Monica Papinski, Edward Schmidt, Alena Pratasouskaya, Dacheng Wang, Rebecca Sullivan, Christopher Bartlett, Joel Weadge, Marc Van der Kamp, Gabriel Moreno-Hagelsieb, Michael Suits, Geoff Horsman

Research output: Contribution to journalArticle (Academic Journal)

1 Citation (Scopus)
194 Downloads (Pure)


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.
Original languageEnglish
Article number3698 (2019)
Number of pages12
JournalNature Communications
Issue number1
Publication statusPublished - 16 Aug 2019


  • Biosynthesis
  • Transferases
  • X-ray crystallography

Fingerprint Dive into the research topics of 'The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis'. Together they form a unique fingerprint.

Cite this