ArticleProceedings of the National Academy of Sciences of the United States of America2010
Identification of the biosynthetic gene cluster for the pacidamycin group of peptidyl nucleoside antibiotics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 102 citations in OpenAlex.
- Tandem-sgRNA Provides an Effective Reverse Genetic Approach for Suppression of Streptomyces Biosynthetic Gene Clusters and Secondary Metabolism.ACS synthetic biology · 2026Article
- Heterologous expression of NRPS and PKS pathways in Escherichia coli: from bottlenecks to biosynthetic platforms.Essays in biochemistry · 2026Review
- Aminoacyl-tRNA-dependent enzymes in natural product biosynthesis: structure-function insights.The Journal of antibiotics · 2026Review
- Controllable Multihalogenation of a Non-native Substrate by the SyrB2 Iron Halogenase.ACS catalysis · 2024Article
- PEARL-Catalyzed Peptide Bond Formation after Chain Reversal by Ureido-Forming Condensation Domains.ACS central science · 2024Article
- TheiScience · 2024Article
- New insights into the dihydro-mureidomycin biosynthesis controlled by two unusual proteins in Streptomyces roseosporus.Microbial cell factories · 2023Article
- Investigation of the potential ofFrontiers in microbiology · 2023Article
- Expanding structural diversity of 5'-aminouridine moiety of sansanmycin via mutational biosynthesis.Frontiers in bioengineering and biotechnology · 2023Article
- Molecular mechanism of mureidomycin biosynthesis activated by introduction of an exogenous regulatory gene ssaA into Streptomyces roseosporus.Science China. Life sciences · 2021Article
- Identification and characterization of enzymes involved in the biosynthesis of pyrimidine nucleoside antibiotics.Natural product reports · 2021Review
- SynBio-SynChem Approaches to Diversifying the Pacidamycins through the Exploitation of an Observed Pictet-Spengler Reaction.Chembiochem : a European journal of chemical biology · 2021Article
- Uridine natural products: Challenging targets and inspiration for novel small molecule inhibitors.Bioorganic & medicinal chemistry · 2020Review
- Mechanism of action of nucleoside antibacterial natural product antibiotics.The Journal of antibiotics · 2019Review
- Recent advances in the biosynthesis of nucleoside antibiotics.The Journal of antibiotics · 2019Review
- Rescrutiny of the sansanmycin biosynthetic gene cluster leads to the discovery of a novel sansanmycin analogue with more potency against Mycobacterium tuberculosis.The Journal of antibiotics · 2019Article
- Cell-free synthetic biology forSynthetic and systems biotechnology · 2018Review
- Analysis of the Pseudouridimycin Biosynthetic Pathway Provides Insights into the Formation of C-nucleoside Antibiotics.Cell chemical biology · 2018Article
- Pac13 is a Small, Monomeric Dehydratase that Mediates the Formation of the 3'-Deoxy Nucleoside of Pacidamycins.Angewandte Chemie (International ed. in English) · 2017Article
- Nonribosomal peptide synthetase biosynthetic clusters of ESKAPE pathogens.Natural product reports · 2017Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Pacidamycins are a family of uridyl tetra/pentapeptide antibiotics that act on the translocase MraY to block bacterial cell wall assembly. To elucidate the biosynthetic logic of pacidamcyins, a putative gene cluster was identified by 454 shotgun genome sequencing of the producer Streptomyces coeruleorubidus NRRL 18370. The 31-kb gene cluster encodes 22 proteins (PacA-V), including highly dissociated nonribosomal peptide synthetase (NRPS) modules and a variety of tailoring enzymes. Gene deletions confirmed that two NRPSs, PacP and PacO, are required for the biosynthesis of pacidamycins. Heterologous expression and in vitro assays of PacL, PacO, and PacP established reversible formation of m-Tyr-AMP, l-Ala-AMP, and diaminopropionyl-AMP, respectively, consistent with the amino acids found in pacidamycin scaffolds. The unusual Ala(4)-Phe(5) dipeptidyl ureido linkage was formed during in vitro assays containing purified PacL, PacJ, PacN, and PacO. Both the genetic and enzymatic studies validate identification of the biosynthetic genes for this subclass of uridyl peptide antibiotics and provide the basis for future mechanistic study of their biosynthesis.
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