ArticleJournal of the American Chemical Society2015
Targeted metagenomics: finding rare tryptophan dimer natural products in the environment.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 61 citations in OpenAlex.
- Advances in natural product discovery: strategies, technologies, and insights.Natural products and bioprospecting · 2026Review
- Benchmarking methods for measuring biosynthetic gene cluster similarity and determination of gene cluster families.Bioinformatics (Oxford, England) · 2025Article
- Expanding the repertoire of imine reductases by mining divergent biosynthetic pathways for promiscuous reactivity.Chem catalysis · 2024Article
- Advances, opportunities, and challenges in methods for interrogating the structure activity relationships of natural products.Natural product reports · 2024Review
- Structure of methyltransferase RedM that forms the dimethylpyrrolinium of the bisindole reductasporine.The Journal of biological chemistry · 2024Article
- Draft genome sequence of potato crop bacterial isolates and nanoparticles-intervention for the induction of secondary metabolites biosynthesis.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Multiplexed mobilization and expression of biosynthetic gene clusters.Nature communications · 2022Article
- Strategies to access biosynthetic novelty in bacterial genomes for drug discovery.Nature reviews. Drug discovery · 2022Review
- Combined assembly of long and short sequencing reads improve the efficiency of exploring the soil metagenome.BMC genomics · 2022Article
- Review
- Metagenome-Guided Analogue Synthesis Yields Improved Gram-Negative-Active Albicidin- and Cystobactamid-Type Antibiotics.Angewandte Chemie (International ed. in English) · 2021Article
- Strategies for Natural Products Discovery from Uncultured Microorganisms.Molecules (Basel, Switzerland) · 2021Review
- Recent Advances in Discovery of Lead Structures from Microbial Natural Products: Genomics- and Metabolomics-Guided Acceleration.Molecules (Basel, Switzerland) · 2021Review
- Cadasides, Calcium-Dependent Acidic Lipopeptides from the Soil Metagenome That Are Active against Multidrug-Resistant Bacteria.Journal of the American Chemical Society · 2019Article
- Concepts and Methods to Access Novel Antibiotics from Actinomycetes.Antibiotics (Basel, Switzerland) · 2018Review
- Bacterial natural product biosynthetic domain composition in soil correlates with changes in latitude on a continent-wide scale.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Interpreting Microbial Biosynthesis in the Genomic Age: Biological and Practical Considerations.Marine drugs · 2017Review
- Using natural products for drug discovery: the impact of the genomics era.Expert opinion on drug discovery · 2017Review
- Phylogeny-guided (meta)genome mining approach for the targeted discovery of new microbial natural products.Journal of industrial microbiology & biotechnology · 2017Review
- Urban park soil microbiomes are a rich reservoir of natural product biosynthetic diversity.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Natural product discovery from environmental genomes (metagenomics) has largely been limited to the screening of existing environmental DNA (eDNA) libraries. Here, we have coupled a chemical-biogeographic survey of chromopyrrolic acid synthase (CPAS) gene diversity with targeted eDNA library production to more efficiently access rare tryptophan dimer (TD) biosynthetic gene clusters. A combination of traditional and synthetic biology-based heterologous expression efforts using eDNA-derived gene clusters led to the production of hydroxysporine (1) and reductasporine (2), two bioactive TDs. As suggested by our phylogenetic analysis of CPAS genes, identified in our survey of crude eDNA extracts, reductasporine (2) contains an unprecedented TD core structure: a pyrrolinium indolocarbazole core that is likely key to its unusual bioactivity profile. This work demonstrates the potential for the discovery of structurally rare and biologically interesting natural products using targeted metagenomics, where environmental samples are prescreened to identify the most phylogenetically unique gene sequences and molecules associated with these genes are accessed through targeted metagenomic library construction and heterologous expression.
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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.