Summary of project PR001996
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001996. The data can be accessed directly via it's Project DOI: 10.21228/M8QH90 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001996 |
| Project DOI: | doi: 10.21228/M8QH90 |
| Project Title: | Integrated multi-omics unveil the impact of the phosphinic compounds, desmethylphosphinothricin and its keto-analogue, on Escherichia coli metabolism |
| Project Summary: | Desmethylphosphinothricin (L-Glu-γ-PH) is the phosphinic analogue of glutamate with a carbon-phosphorus (C-P) bond. In L-Glu-γ-PH the phosphinic group acts as a bioisostere of glutamate γ-carboxyl group allowing the molecule to be a substrate of Escherichia coli glutamate decarboxylase, a pyridoxal 5’-phosphate (PLP)-dependent α-decarboxylase. In addition, the L-Glu-γ-PH decarboxylation product, GABA-PH, is further metabolized by bacterial GABA-transaminase, another PLP-dependent enzyme, and succinic semialdehyde dehydrogenease, a NADP+ -dependent enzyme. The product of these consecutive reactions, the so-called GABA shunt, lead to the formation of succinate-PH, the phosphinic analogue of succinate, a TCA cycle intermediate. Notably, L-Glu-γ-PH displays an antibacterial activity of the same order of well-established antibiotics in E. coli. The dipeptide L-Leu-Glu-γ-PH was shown to display a higher efficacy, likely as a consequence of an improved penetration into the bacteria. Herein, with the aim of further understanding the intracellular effects of L-Glu-γ-PH, 1H NMR-based metabolomics and LC-MS-based shotgun proteomics were used. This study included also the keto-analogue of L-Glu-γ-PH, α-ketoglutarate-γ-PH (α-KG-γ-PH), which also exhibits antimicrobial activity. L-Glu-γ-PH and α-KG-γ-PH were found to similarly impact the bacterial metabolism, though the overall effect of α-KG-γ-PH is more pervasive, and not exclusively because of its intracellular conversion into L-Glu-γ-PH. Notably, both molecules impact the pathways where aspartate, glutamate and glutamine are used as precursors for the biosynthesis of related metabolites, activate the acid stress response and deprive cells of nitrogen. This work highlights the multi-target drug potential of L-Glu-γ-PH and α-KG-γ-PH and paves the way for their exploitation as antimicrobials. |
| Institute: | ITQB NOVA |
| Last Name: | Gonçalves |
| First Name: | Luís G |
| Address: | Avenida Republica, Oeiras, Not USCanada, 2780-157 Oeiras, Portugal |
| Email: | lgafeira@itqb.unl.pt |
| Phone: | 214469464 |
Summary of all studies in project PR001996
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003202 | Integrated multi-omics unveil the impact of the phosphinic compounds, desmethylphosphinothricin and its keto-analogue, on Escherichia coli metabolism | Escherichia coli | ITQB NOVA | NMR | 2024-08-08 | 1 | 29 | Uploaded data (40.2M)* |
