ArticleNature2015
β-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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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.
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Who cites it
51 citing papers in PubMed, 113 citations in OpenAlex.
- A rational multi-target combination strategy for synergistic improvement of non-ribosomal peptide production.Nature communications · 2025Article
- PEARL-Catalyzed Peptide Bond Formation after Chain Reversal by Ureido-Forming Condensation Domains.ACS central science · 2024Article
- The structure of the monobactam-producing thioesterase domain of SulM forms a unique complex with the upstream carrier protein domain.bioRxiv : the preprint server for biology · 2024Article
- TheiScience · 2024Article
- Dehydroamino acid residues in bioactive natural products.Natural product reports · 2024Review
- Whole genome analysis, detoxification of ochratoxin a and physiological characterization of a novelFrontiers in microbiology · 2024Article
- Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases.Natural product reports · 2023Review
- Biosynthesis of Antifungal Solanimycin May Involve an Iterative Nonribosomal Peptide Synthetase Module.ACS chemical biology · 2023Article
- Selective Synthesis of Lysine Peptides and the Prebiotically Plausible Synthesis of Catalytically Active Diaminopropionic Acid Peptide Nitriles in Water.Journal of the American Chemical Society · 2023Article
- Research progress and future prospects of antimicrobial modified polyetheretherketone (PEEK) for the treatment of bone infections.Frontiers in bioengineering and biotechnology · 2023Review
- Structural Studies of Modular Nonribosomal Peptide Synthetases.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Accurate Substrate-Like Probes for Trapping Late-Stage Intermediates in Nonribosomal Peptide Synthetase Condensation Domains.ACS chemical biology · 2022Article
- Enzymatic assembly of the salinosporamide γ-lactam-β-lactone anticancer warhead.Nature chemical biology · 2022Article
- Aminoacyl chain translocation catalysed by a type II thioesterase domain in an unusual non-ribosomal peptide synthetase.Nature communications · 2022Article
- The ABCT31 Transporter Regulates the Export System of Phenylacetic Acid as a Side-Chain Precursor of Penicillin G inFrontiers in microbiology · 2022Article
- BioCAT: Search for biosynthetic gene clusters producing nonribosomal peptides with known structure.Computational and structural biotechnology journal · 2022Article
- Genome mining methods to discover bioactive natural products.Natural product reports · 2021Review
- Nonribosomal peptide synthetases and their biotechnological potential in Penicillium rubens.Journal of industrial microbiology & biotechnology · 2021Review
- Competing off-loading mechanisms of meropenem from an l,d-transpeptidase reduce antibiotic effectiveness.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Caerulomycin and collismycin antibiotics share a trans-acting flavoprotein-dependent assembly line for 2,2'-bipyridine formation.Nature communications · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Non-ribosomal peptide synthetases are giant enzymes composed of modules that house repeated sets of functional domains, which select, activate and couple amino acids drawn from a pool of nearly 500 potential building blocks. The structurally and stereochemically diverse peptides generated in this manner underlie the biosynthesis of a large sector of natural products. Many of their derived metabolites are bioactive such as the antibiotics vancomycin, bacitracin, daptomycin and the β-lactam-containing penicillins, cephalosporins and nocardicins. Penicillins and cephalosporins are synthesized from a classically derived non-ribosomal peptide synthetase tripeptide (from δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine synthetase). Here we report an unprecedented non-ribosomal peptide synthetase activity that both assembles a serine-containing peptide and mediates its cyclization to the critical β-lactam ring of the nocardicin family of antibiotics. A histidine-rich condensation domain, which typically performs peptide bond formation during product assembly, also synthesizes the embedded four-membered ring. We propose a mechanism, and describe supporting experiments, that is distinct from the pathways that have evolved to the three other β-lactam antibiotic families: penicillin/cephalosporins, clavams and carbapenems. These findings raise the possibility that β-lactam rings can be regio- and stereospecifically integrated into engineered peptides for application as, for example, targeted protease inactivators.
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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.