Whole-Cell Detection of C-P Bonds in Bacteria.
Christopher BartlettSonal BansalAlysha BurnettMichael D SuitsJacob SchaeferLynette CegelskiGeoff P HorsmanJoel T WeadgePublished in: Biochemistry (2017)
Naturally produced molecules possessing a C-P bond, such as phosphonates and phosphinates, remain vastly underexplored. Although success stories like fosfomycin have reinvigorated small molecule phosphonate discovery efforts, bioinformatic analyses predict an enormous unexplored biological reservoir of C-P bond-containing molecules, including those attached to complex macromolecules. However, high polarity, a lack of chromophores, and complex macromolecular association impede phosphonate discovery and characterization. Here we detect widespread transcriptional activation of phosphonate biosynthetic machinery across diverse bacterial phyla and describe the use of solid-state nuclear magnetic resonance to detect C-P bonds in whole cells of representative Gram-negative and Gram-positive bacterial species. These results suggest that phosphonate tailoring is more prevalent than previously recognized and set the stage for elucidating the fascinating chemistry and biology of these modifications.
Keyphrases
- gram negative
- small molecule
- multidrug resistant
- solid state
- magnetic resonance
- protein protein
- induced apoptosis
- transition metal
- high throughput
- single cell
- cell therapy
- gene expression
- cell cycle arrest
- transcription factor
- signaling pathway
- oxidative stress
- stem cells
- magnetic resonance imaging
- pi k akt
- drug discovery
- cell death
- cell proliferation
- bone marrow
- electron transfer