ArticleAngewandte Chemie (International ed. in English)2019
Biosynthesis of l-4-Chlorokynurenine, an Antidepressant Prodrug and a Non-Proteinogenic Amino Acid Found in Lipopeptide Antibiotics.
Article in Angewandte Chemie (International ed. in English), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Growth-coupled microbial biosynthesis of the animal pigment xanthommatin.Nature biotechnology · 2026Article
- DeepHalo: Deep learning-powered exploration of halogenated metabolites uncovering antibacterial depsipeptides.Acta pharmaceutica Sinica. B · 2026Article
- Discovery of the 5-Chlorokynurenine Pathway in Lodopyridone Biosynthesis.Journal of natural products · 2026Article
- Break it to make it: Rewiring bacterial metabolism for the growth-coupled biosynthesis of xanthommatin animal pigments.Chem catalysis · 2026Article
- Discovery and Functional Characterization of SnFDHal, an Efficient Tryptophan 5-Halogenase from Streptomyces noursei.Applied biochemistry and biotechnology · 2026Article
- Structural Basis of Regioselective Bromination of Tricyclic Tryptoline by the Tryptophan Halogenase Thal.Chembiochem : a European journal of chemical biology · 2025Article
- Crystallographic and Thermodynamic Evidence of Negative Coupling in the Flavin-Dependent Tryptophan Halogenases AbeH and BorH.ACS omega · 2025Article
- Genomics-Driven Discovery of Plantariitin A, a New Lipopeptide inMolecules (Basel, Switzerland) · 2025Article
- Peptide halogenation biochemistry: interfacing pharmaceutical deliverables with chemical innovation.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2025Review
- A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules.Nature communications · 2024Article
- Kynurenines, Neuronal Excitotoxicity, and Mitochondrial Oxidative Stress: Role of the Intestinal Flora.International journal of molecular sciences · 2024Review
- Modern Trends in Natural Antibiotic Discovery.Life (Basel, Switzerland) · 2023Review
- Redox Biocatalysis: Quantitative Comparisons of Nicotinamide Cofactor Regeneration Methods.ChemSusChem · 2022Review
- The Microbiota-Gut-Brain Axis in Depression: The Potential Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect.Nutrients · 2022Review
- Discovery of unusual dimeric piperazyl cyclopeptides encoded by aProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Halogenases: a palette of emerging opportunities for synthetic biology-synthetic chemistry and C-H functionalisation.Chemical Society reviews · 2021Review
- Genomic Determinants Encode the Reactivity and Regioselectivity of Flavin-Dependent Halogenases in Bacterial Genomes and Metagenomes.mSystems · 2021Article
- Structure of apo flavin-dependent halogenase Xcc4156 hints at a reason for cofactor-soaking difficulties.Acta crystallographica. Section D, Structural biology · 2020Article
- Discovery of Kynurenines Containing Oligopeptides as Potent Opioid Receptor Agonists.Biomolecules · 2020Article
- Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds.Frontiers in bioengineering and biotechnology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
l-4-Chlorokynurenine (l-4-Cl-Kyn) is a neuropharmaceutical drug candidate that is in development for the treatment of major depressive disorder. Recently, this amino acid was naturally found as a residue in the lipopeptide antibiotic taromycin. Herein, we report the unprecedented conversion of l-tryptophan into l-4-Cl-Kyn catalyzed by four enzymes in the taromycin biosynthetic pathway from the marine bacterium Saccharomonospora sp. CNQ-490. We used genetic, biochemical, structural, and analytical techniques to establish l-4-Cl-Kyn biosynthesis, which is initiated by the flavin-dependent tryptophan chlorinase Tar14 and its flavin reductase partner Tar15. This work revealed the first tryptophan 2,3-dioxygenase (Tar13) and kynurenine formamidase (Tar16) enzymes that are selective for chlorinated substrates. The substrate scope of Tar13, Tar14, and Tar16 was examined and revealed intriguing promiscuity, thereby opening doors for the targeted engineering of these enzymes as useful biocatalysts.
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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.