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The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis.

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.

SUBMITTER: Rice K

PROVIDER: S-EPMC6697681 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis.

Rice Kyle K Batul Kissa K Whiteside Jacqueline J Kelso Jayne J Papinski Monica M Schmidt Edward E Pratasouskaya Alena A Wang Dacheng D Sullivan Rebecca R Bartlett Christopher C Weadge Joel T JT Van der Kamp Marc W MW Moreno-Hagelsieb Gabriel G Suits Michael D MD Horsman Geoff P GP

Nature communications 20190816 1

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 t ...[more]

PMID: 31420548

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The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis.

Publications

The predominance of nucleotidyl activation in bacterial phosphonate biosynthesis.

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