|
type |
Journal Article |
authors |
Rice K, Batul K, Whiteside J, Kelso J, Papinski M, Schmidt E, Pratasouskaya A, Wang D, Sullivan R, Bartlett C, Weadge JT, Van der Kamp MW, Moreno-Hagelsieb G, Suits MD, Horsman GP
|
title |
The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis |
journal |
Nat Commun |
Activity |
2.6.1.37 |
Family |
2.6.1.37 |
sel |
selected |
ui |
31420548 |
year |
(2019) |
volume |
10 |
number |
1 |
pages |
3698 |
| |
keywords |
DOI: 10.1038/s41467-019-11627-6 |
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. |
last changed |
2019/08/21 15:00 |
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