Summary of project PR001267
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 PR001267. The data can be accessed directly via it's Project DOI: 10.21228/M8XX3Q This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001267 |
| Project DOI: | doi: 10.21228/M8XX3Q |
| Project Title: | Mutasynthetic production and antimicrobial characterisation of Darobactin darobactin analogs_NMR analysis |
| Project Summary: | There is great need for therapeutics against multi-drug resistant, Gram-negative bacterial pathogens. Recently, darobactin A, a novel bicyclic heptapeptide that selectively kills Gram-negative bacteria by targeting the outer-membrane protein BamA, was discovered. Its efficacy was proven in animal infection models of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, thus promoting darobactin A as a promising lead compound. Originally discovered from members of the nematode symbiotic genus Photorhabdus, the biosynthetic gene cluster (BGC) encoding for the synthesis of darobactin A can also be found in other γ-proteobacterial families. Therein, the precursor peptides DarB-F, which differ in their core sequence from darobactin A, were identified in silico. Even though production of these analogs was not observed in the putative producer strains, we were able to generate them by mutasynthetic derivatization of a heterologous expression system. The generated analogs were isolated and tested for their bioactivity. The most potent compound, darobactin B, was used for co-crystallization with the target BamA, revealing an identical binding site to darobactin A. Besides its potency, darobactin B did not exhibit cytotoxicity and was slightly more active against Acinetobacter baumanii isolates than darobactin A. Furthermore, we evaluated the plasma protein binding of darobactin A and B, indicating their different pharmacokinetic properties. This is the first report on new members of this new antibiotics class, which is likely to expand to several promising therapeutic candidates |
| Institute: | Justus-Liebig-University Giessen |
| Laboratory: | Schäberle Laboratory |
| Last Name: | Mettal |
| First Name: | Ute |
| Address: | Ohlebergsweg 12, 35392 Giessen, Germany |
| Email: | Ute.Mettal@chemie.uni-giessen.de |
| Phone: | +49 641 97219 142 |
| Publications: | Mutasynthetic production and antimicrobial characterisation of Ddarobactin analogs |
| Contributors: | Nils Böhringer, Robert Green, Yang Liu, Ute Mettal, Michael Marner, Seyed Majed Modaresi, Roman P. Jakob, Zerlina G. Wuisan, Timm Maier, Akira Iinishi, Sebastian Hiller, Kim Lewis, Till F. Schäberle |
Summary of all studies in project PR001267
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001994 | Mutasynthetic production and antimicrobial characterisation of Darobactin darobactin analogs (NMR analysis) | Escherichia coli | Justus-Liebig-University Giessen | NMR | 2022-11-21 | 1 | 6 | Uploaded data (388.7M)* |
| ST001995 | Mutasynthetic production and antimicrobial characterisation of Darobactin darobactin analogs (MS analysis) | Escherichia coli | Justus-Liebig-University Giessen | MS | 2022-11-21 | 1 | 6 | Uploaded data (6.8G)* |
