ArticleProceedings of the National Academy of Sciences of the United States of America2013
Revisiting the biosynthesis of dehydrophos reveals a tRNA-dependent pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Late-Stage Posttranslational Assembly of Fosfazinomycins.bioRxiv : the preprint server for biology · 2026Article
- From Discovery to Manufacturing: A Quantitative Review of Phosphonates and Strategies for High-Titer Production.Microorganisms · 2026Review
- Aminoacyl-tRNA-dependent enzymes in natural product biosynthesis: structure-function insights.The Journal of antibiotics · 2026Review
- Identification of Two Distinct Stereoselective Lysine 5-Hydroxylases by Genome Mining Based on Alazopeptin Biosynthetic Enzymes.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Determining biosynthetic gene cluster boundaries through comparative bioinformatics.Methods in enzymology · 2025Article
- Streptomyces lividans 66 produces a protease inhibitor via a tRNA-utilizing enzyme interacting with a C-minus NRPS.Journal of industrial microbiology & biotechnology · 2023Article
- Article
- An Unusual Oxidative Rearrangement Catalyzed by a Divergent Member of the 2-Oxoglutarate-Dependent Dioxygenase Superfamily during Biosynthesis of Dehydrofosmidomycin.Angewandte Chemie (International ed. in English) · 2022Article
- Biosynthesis of Argolaphos Illuminates the Unusual Biochemical Origins of Aminomethylphosphonate and NJournal of the American Chemical Society · 2022Article
- Small-Molecule Acetylation by GCN5-RelatedMicrobiology and molecular biology reviews : MMBR · 2020Review
- Nonribosomal Peptide Extension by a Peptide Amino-Acyl tRNA Ligase.Journal of the American Chemical Society · 2019Article
- Use of the dehydrophos biosynthetic enzymes to prepare antimicrobial analogs of alaphosphin.Organic & biomolecular chemistry · 2019Article
- Recent examples of α-ketoglutarate-dependent mononuclear non-haem iron enzymes in natural product biosyntheses.Natural product reports · 2018Review
- Investigation of Amide Bond Formation during Dehydrophos Biosynthesis.ACS chemical biology · 2018Article
- Deciphering the tRNA-dependent lipid aminoacylation systems in bacteria: Novel components and structural advances.RNA biology · 2018Review
- Cameo appearances of aminoacyl-tRNA in natural product biosynthesis.Current opinion in chemical biology · 2016Review
- tRNA-Dependent Aminoacylation of an Amino Sugar Intermediate in the Biosynthesis of a Streptothricin-Related Antibiotic.Applied and environmental microbiology · 2016Article
- Discovery of phosphonic acid natural products by mining the genomes of 10,000 actinomycetes.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Biosynthesis of fosfazinomycin is a convergent process.Chemical science · 2015Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Bioactive natural products containing a C-P bond act as mimics of phosphate esters and carboxylic acids, thereby competing with these compounds for active sites of enzymes. Dehydrophos (DHP), a broad-spectrum antibiotic, is a phosphonotripeptide produced by Streptomyces luridus, in which glycine and leucine are linked to an aminophosphonate analog of dehydroalanine, ΔAla(P). This unique feature, in combination with the monomethylation of the phosphonic acid, renders DHP a Trojan horse type antibiotic because peptidase-mediated hydrolysis will release methyl acetylphosphonate, a potent inhibitor of pyruvate dehydrogenase. Bioinformatic analysis of the biosynthetic gene cluster suggested that ΔAla(P) would be generated from Ser(P), the phosphonate analog of Ser, by phosphorylation and subsequent elimination, and that ΔAla(P) would be condensed with Leu-tRNA(Leu). DhpH was anticipated to carry out this elimination/ligation cascade. DhpH is a multidomain protein, in which a pyridoxal phosphate binding domain is fused to an N-acetyltransferase domain related to the general control nonderepressible-5 (GCN5) family. In this work, the activity of DhpH was reconstituted in vitro. The enzyme was able to catalyze the β-elimination reaction of pSer(P) to generate ΔAla(P), but it was unable to condense ΔAla(P) with Leu. Instead, ΔAla(P) is hydrolyzed to acetyl phosphonate, which is converted to Ala(P) by a second pyridoxal phosphate-dependent enzyme, DhpD. Ala(P) is the substrate for the condensation with Leu-tRNA(Leu) catalyzed by the C-terminal domain of DhpH. DhpJ, a 2-oxoglutarate/Fe(II)-dependent enzyme, introduces the vinyl functionality into Leu-Ala(P) acting as a desaturase, and addition of Gly by DhpK in a Gly-tRNA(Gly)-dependent manner completes the in vitro biosynthesis of dehydrophos.
Indexed as
Identifiers
What OpenQuestion holds
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.