ArticleProceedings of the National Academy of Sciences of the United States of America2015
Discovery of phosphonic acid natural products by mining the genomes of 10,000 actinomycetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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102 citing papers in PubMed, 209 citations in OpenAlex.
- From Discovery to Manufacturing: A Quantitative Review of Phosphonates and Strategies for High-Titer Production.Microorganisms · 2026Review
- Discovery of the Phosphonate Flavophos Produced byJournal of the American Chemical Society · 2026Article
- Biocatalytic Tetrapeptide Macrocyclization by Cryptic Penicillin-Binding Protein-Type Thioesterases.Biochemistry · 2026Article
- Discovery of the Phosphonate Flavophos Produced bybioRxiv : the preprint server for biology · 2026Article
- A Dynamic Gate Enables Regioselective Hydroxylation of Free Arginine by a Non-Canonical Heme Enzyme.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Biocatalytic cascade for the synthesis of methylphosphonate from phosphoenolpyruvate.Microbial cell factories · 2025Article
- Recent advances in natural and synthetic phosphonate therapeutics.Current opinion in microbiology · 2025Review
- New antifungal breaks the mould.Nature · 2025Article
- Determining biosynthetic gene cluster boundaries through comparative bioinformatics.Methods in enzymology · 2025Article
- Phosphonates ofInternational journal of molecular sciences · 2024Article
- Integrated multi-omics unveil the impact of H-phosphinic analogs of glutamate and α-ketoglutarate on Escherichia coli metabolism.The Journal of biological chemistry · 2024Article
- Phosphonoalamides Reveal the Biosynthetic Origin of Phosphonoalanine Natural Products and a Convergent Pathway for Their Diversification.Angewandte Chemie (International ed. in English) · 2024Article
- Biosynthesis ofACS chemical biology · 2024Article
- Elucidation of unusual biosynthesis and DnaN-targeting mode of action of potent anti-tuberculosis antibiotics Mycoplanecins.Nature communications · 2024Article
- Exploitation of microbial activities at low pH to enhance planetary health.FEMS microbiology reviews · 2024Article
- Discovery of Streptomyces species CS-62, a novel producer of the Acinetobacter baumannii selective antibiotic factumycin.Journal of industrial microbiology & biotechnology · 2024Article
- Challenging old microbiological treasures for natural compound biosynthesis capacity.Frontiers in bioengineering and biotechnology · 2024Article
- Comparative genomics of the niche-specific plant pathogenApplied and environmental microbiology · 2023Article
- Bioprospecting of unexplored halophilic actinobacteria against human infectious pathogens.3 Biotech · 2023Review
42 more citing papers are in PubMed but not listed here.
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17 authors at 2 institutions in 2 countries.
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Abstract
Although natural products have been a particularly rich source of human medicines, activity-based screening results in a very high rate of rediscovery of known molecules. Based on the large number of natural product biosynthetic genes in microbial genomes, many have proposed "genome mining" as an alternative approach for discovery efforts; however, this idea has yet to be performed experimentally on a large scale. Here, we demonstrate the feasibility of large-scale, high-throughput genome mining by screening a collection of over 10,000 actinomycetes for the genetic potential to make phosphonic acids, a class of natural products with diverse and useful bioactivities. Genome sequencing identified a diverse collection of phosphonate biosynthetic gene clusters within 278 strains. These clusters were classified into 64 distinct groups, of which 55 are likely to direct the synthesis of unknown compounds. Characterization of strains within five of these groups resulted in the discovery of a new archetypical pathway for phosphonate biosynthesis, the first (to our knowledge) dedicated pathway for H-phosphinates, and 11 previously undescribed phosphonic acid natural products. Among these compounds are argolaphos, a broad-spectrum antibacterial phosphonopeptide composed of aminomethylphosphonate in peptide linkage to a rare amino acid N(5)-hydroxyarginine; valinophos, an N-acetyl l-Val ester of 2,3-dihydroxypropylphosphonate; and phosphonocystoximate, an unusual thiohydroximate-containing molecule representing a new chemotype of sulfur-containing phosphonate natural products. Analysis of the genome sequences from the remaining strains suggests that the majority of the phosphonate biosynthetic repertoire of Actinobacteria has been captured at the gene level. This dereplicated strain collection now provides a reservoir of numerous, as yet undiscovered, phosphonate natural products.
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