ArticleAngewandte Chemie (International ed. in English)2017
Biosynthesis of the Enterotoxic Pyrrolobenzodiazepine Natural Product Tilivalline.
Article in Angewandte Chemie (International ed. in English), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules.Cell host & microbe · 2025Pooled it
- Novel bacteriumGut microbes · 2026Article
- TagR, a newly identified member of the MarR family of transcriptional regulators, represses the NRPS operon inMicrobiology spectrum · 2026Article
- ExpoLib: a framework for an MS/MS exposome library of anthropogenic and natural toxicants and their biotransformation products.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- The Quorum-Sensing Regulator SdiA ActivatesMicroorganisms · 2026Article
- Chemokine-receptor-dependent inflammatory responses contribute to two-hit-induced experimental necrotizing enterocolitis and represent a potential therapeutic target.Frontiers in immunology · 2026Article
- Protein Engineering of Biosynthetic Enzymes Unlocks Libraries of Bioactive Tilimycin Analogs.ACS catalysis · 2025Article
- Leveraging chemical synthesis to discover metabolites from the gut microbiome.Annals of the New York Academy of Sciences · 2025Review
- An efficient lysate-based approach for biosynthesis of the pyrrolobenzodiazepine natural product tilimycin.Journal of biotechnology · 2025Article
- Exploring the bioactive landscape: peptides and non-peptides from the human microbiota.NPJ biofilms and microbiomes · 2025Review
- Bacterial small molecule metabolites implicated in gastrointestinal cancer development.Nature reviews. Microbiology · 2025Review
- Article
- The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production inMicroorganisms · 2025Article
- The Nucleoid Proteins Fis and IHF Positively Regulate the Gene Expression of Operons Responsible for Producing the Cytotoxins Tilimycin and Tilivalline inInternational journal of microbiology · 2025Article
- Microbiota regulates neonatal disease tolerance to virus-evoked necrotizing enterocolitis by shaping the STAT1-NLRC5 axis in the intestinal epithelium.Cell host & microbe · 2024Article
- Mining metagenomic data to gain a new insight into the gut microbial biosynthetic potential in placental mammals.Microbiology spectrum · 2024Article
- Core genome multilocus sequence typing (cgMLST) applicable to the monophyleticJournal of clinical microbiology · 2024Article
- Lipophilic arsenic compounds in the cultured green alga Chlamydomonas reinhardtii.Analytical and bioanalytical chemistry · 2024Article
- Country-wide expansion of a VIM-1 carbapenemase-producing Klebsiella oxytoca ST145 lineage in Poland, 2009-2019.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023Article
- Genome mining reveals novel biosynthetic gene clusters in entomopathogenic bacteria.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nonribosomal enterotoxin tilivalline was the first naturally occurring pyrrolobenzodiazepine to be linked to disease in the human intestine. Since the producing organism Klebsiella oxytoca is part of the intestinal microbiota and the pyrrolobenzodiazepine causes the pathogenesis of colitis it is important to understand the biosynthesis and regulation of tilivalline activity. Here we report the biosynthesis of tilivalline and show that this nonribosomal peptide assembly pathway initially generates tilimycin, a simple pyrrolobenzodiazepine with cytotoxic properties. Tilivalline results from the non-enzymatic spontaneous reaction of tilimycin with biogenetically generated indole. Through a chemical total synthesis of tilimycin we could corroborate the predictions made about the biosynthesis. Production of two cytotoxic pyrrolobenzodiazepines with distinct functionalities by human gut resident Klebsiella oxytoca has important implications for intestinal disease.
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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.