ArticleAngewandte Chemie (International ed. in English)2023
Darobactins Exhibiting Superior Antibiotic Activity by Cryo-EM Structure Guided Biosynthetic Engineering.
Article in Angewandte Chemie (International ed. in English), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed.
- Integration of Membrane Proteins into the Outer Membrane of Diderm Bacteria by the BAM Complex.Chemical reviews · 2026Review
- Targeting of the Gram-Negative Outer Membrane for Antibiotic Discovery and Potentiation.ACS infectious diseases · 2026Review
- Synthetic Studies Towards Darobactin A.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Molecular mechanism of action of small molecule SMT-738 on bacterial lipoprotein transporter LolCDE.Nature communications · 2026Article
- Exploiting Pharmacokinetic/Pharmacodynamic Methods for Optimizing and Accelerating Drug Development of Innovative Anti-Infectives.ChemMedChem · 2026Review
- Expanding the Range of Darobactin Derivatives by Amber Stop Codon Suppression To Introduce Non-canonical Amino Acids.ACS omega · 2025Article
- Antibacterial macrocyclic peptides reveal a distinct mode of BamA inhibition.Nature communications · 2025Article
- Natural peptides and their synthetic congeners acting againstRSC medicinal chemistry · 2025Review
- Aromatic side-chain crosslinking in RiPP biosynthesis.Nature chemical biology · 2025Review
- In Vivo Activity Profiling of Biosynthetic Darobactin D22 against Critical Gram-Negative Pathogens.ACS infectious diseases · 2024Article
- Thermo-amplifier circuit in probiotic E. coli for stringently temperature-controlled release of a novel antibiotic.Journal of biological engineering · 2024Article
- Article
- Harnessing Gram-negative bacteria for novel anti-Gram-negative antibiotics.Microbial biotechnology · 2024Review
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Sophisticated natural products as antibiotics.Nature · 2024Review
- Darobactin Substrate Engineering and Computation Show Radical Stability Governs Ether versus C-C Bond Formation.Journal of the American Chemical Society · 2024Article
- Discovery and engineering of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products.RSC chemical biology · 2024Review
- ATP-independent assembly machinery of bacterial outer membranes: BAM complex structure and function set the stage for next-generation therapeutics.Protein science : a publication of the Protein Society · 2024Review
- Tackling the outer membrane: facilitating compound entry into Gram-negative bacterial pathogens.npj antimicrobials and resistance · 2023Review
- New Genetically Engineered Derivatives of Antibacterial Darobactins Underpin Their Potential for Antibiotic Development.Journal of medicinal chemistry · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Over recent decades, the pipeline of antibiotics acting against Gram-negative bacteria is running dry, as most discovered candidate antibiotics suffer from insufficient potency, pharmacokinetic properties, or toxicity. The darobactins, a promising new small peptide class of drug candidates, bind to novel antibiotic target BamA, an outer membrane protein. Previously, we reported that biosynthetic engineering in a heterologous host generated novel darobactins with enhanced antibacterial activity. Here we utilize an optimized purification method and present cryo-EM structures of the Bam complex with darobactin 9 (D9), which served as a blueprint for the biotechnological generation of twenty new darobactins including halogenated analogs. The newly engineered darobactin 22 binds more tightly to BamA and outperforms the favorable activity profile of D9 against clinically relevant pathogens such as carbapenem-resistant Acinetobacter baumannii up to 32-fold, without observing toxic effects.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.