ArticleCell chemical biology2018
Analysis of the Pseudouridimycin Biosynthetic Pathway Provides Insights into the Formation of C-nucleoside Antibiotics.
Article in Cell chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
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- Biosynthesis and Genome Mining Potentials of Nucleoside Natural Products.Chembiochem : a European journal of chemical biology · 2023Article
- Pseudouridine-Modifying Enzymes SapB and SapH Control Entry into the Pseudouridimycin Biosynthetic Pathway.ACS chemical biology · 2023Article
- Experimental and computational snapshots of C-C bond formation in a C-nucleoside synthase.Open biology · 2023Article
- Reference-Grade Genome and Large Linear Plasmid of Streptomyces rimosus: Pushing the Limits of Nanopore Sequencing.Microbiology spectrum · 2022Article
- Biosynthesis of C-nucleoside antibiotics in actinobacteria: recent advances and future developments.Microbial cell factories · 2022Review
- Identification and characterization of enzymes involved in the biosynthesis of pyrimidine nucleoside antibiotics.Natural product reports · 2021Review
- Effective approaches to discover new microbial metabolites in a large strain library.Journal of industrial microbiology & biotechnology · 2021Review
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- Blocks in the pseudouridimycin pathway unlock hidden metabolites in the Streptomyces producer strain.Scientific reports · 2021Article
- Cryptic phosphorylation in nucleoside natural product biosynthesis.Nature chemical biology · 2021Article
- Heterologous Expression of Pseudouridimycin and Description of the Corresponding Minimal Biosynthetic Gene Cluster.Molecules (Basel, Switzerland) · 2021Article
- Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Pseudouridimycin (PUM) is a selective nucleoside-analog inhibitor of bacterial RNA polymerase with activity against Gram-positive and Gram-negative bacteria. PUM, produced by Streptomyces sp. ID38640, consists of a formamidinylated, N-hydroxylated Gly-Gln dipeptide conjugated to 5'-aminopseudouridine. We report the characterization of the PUM gene cluster. Bioinformatic analysis and mutational knockouts of pum genes with analysis of accumulated intermediates, define the PUM biosynthetic pathway. The work provides the first biosynthetic pathway of a C-nucleoside antibiotic and reveals three unexpected features: production of free pseudouridine by the dedicated pseudouridine synthase, PumJ; nucleoside activation by specialized oxidoreductases and aminotransferases; and peptide-bond formation by amide ligases. A central role in the PUM biosynthetic pathway is played by the PumJ, which represents a divergent branch within the TruD family of pseudouridine synthases. PumJ-like sequences are associated with diverse gene clusters likely to govern the biosynthesis of different classes of C-nucleoside antibiotics.
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