ArticleProceedings of the National Academy of Sciences of the United States of America2013
Discovery of indolotryptoline antiproliferative agents by homology-guided metagenomic screening.
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 51 papers.
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Who cites it
51 citing papers in PubMed, 112 citations in OpenAlex.
- Bacterial biosynthetic superclusters: emerging drivers of synergistic natural products against antimicrobial resistance.Essays in biochemistry · 2026Review
- The X-Ray Crystal Structure of BorF, the Flavin Reductase Subunit of a Two-Component Flavin-Dependent Tryptophan Halogenase.Proteins · 2026Article
- A reversible broad-spectrum antiviral targets the human V-ATPase VResearch square · 2026Article
- Benchmarking methods for measuring biosynthetic gene cluster similarity and determination of gene cluster families.Bioinformatics (Oxford, England) · 2025Article
- Metagenomics and its impact on environmental and therapeutic microbiology.Archives of microbiology · 2025Review
- Structural and functional analysis of SAM-dependent N-methyltransferases involved in ovoselenol and ovothiol biosynthesis.Structure (London, England : 1993) · 2025Article
- Crystallographic and Thermodynamic Evidence of Negative Coupling in the Flavin-Dependent Tryptophan Halogenases AbeH and BorH.ACS omega · 2025Article
- Metagenomics approaches in the discovery and development of new bioactive compound of 8-demethoxy-10-deoxysteffimycin from mangrove sediments.3 Biotech · 2024Article
- Advances, opportunities, and challenges in methods for interrogating the structure activity relationships of natural products.Natural product reports · 2024Review
- Comprehensive genome analysis of two novelFrontiers in microbiology · 2024Article
- A novel class of broad-spectrum active-site-directed 3C-like protease inhibitors with nanomolar antiviral activity against highly immune-evasive SARS-CoV-2 Omicron subvariants.Emerging microbes & infections · 2023Article
- Naturally Occurring Organohalogen Compounds-A Comprehensive Review.Progress in the chemistry of organic natural products · 2023Review
- Identification of PKS Gene Clusters from Metagenomic Libraries Using a Next-Generation Sequencing Approach.Methods in molecular biology (Clifton, N.J.) · 2023Article
- 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
- Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds.Frontiers in bioengineering and biotechnology · 2020Review
- Discovery of Novel Biosynthetic Gene Cluster Diversity From a Soil Metagenomic Library.Frontiers in microbiology · 2020Article
- Novel bioactive natural products from bacteria via bioprospecting, genome mining and metabolic engineering.Microbial biotechnology · 2019Review
- Biosynthesis of l-4-Chlorokynurenine, an Antidepressant Prodrug and a Non-Proteinogenic Amino Acid Found in Lipopeptide Antibiotics.Angewandte Chemie (International ed. in English) · 2019Article
- Heterologous expression-facilitated natural products' discovery in actinomycetes.Journal of industrial microbiology & biotechnology · 2019Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Natural product discovery by random screening of broth extracts derived from cultured bacteria often suffers from high rates of redundant isolation, making it ever more challenging to identify novel biologically interesting natural products. Here we show that homology-based screening of soil metagenomes can be used to specifically target the discovery of new members of traditionally rare, biomedically relevant natural product families. Phylogenetic analysis of oxy-tryptophan dimerization gene homologs found within a large soil DNA library enabled the identification and recovery of a unique tryptophan dimerization biosynthetic gene cluster, which we have termed the bor cluster. When heterologously expressed in Streptomyces albus, this cluster produced an indolotryptoline antiproliferative agent with CaMKIIδ kinase inhibitory activity (borregomycin A), along with several dihydroxyindolocarbazole anticancer/antibiotics (borregomycins B-D). Similar homology-based screening of large environmental DNA libraries is likely to permit the directed discovery of new members within other previously rare families of bioactive natural products.
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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.