ArticleCommunications biology2024
Exploring a general multi-pronged activation strategy for natural product discovery in Actinomycetes.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Regulatory and metabolic control of microbial biosynthetic gene clusters.Communications biology · 2026Review
- Secondary metabolite profiling of rare Micromonospora spp. from cold desert of NW Himalayas via multi-omics analysis.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Accelerating natural product discovery with linked MS-genomics and language/transformer-based models.npj antimicrobials and resistance · 2026Article
- Enhancing Secondary Metabolite Production in Actinobacteria Through Over-Expression of a Medium-Sized SARP Regulator.International journal of molecular sciences · 2025Article
- Emerging strategies to enhance microbial natural product-based drug discovery.Current opinion in biotechnology · 2025Review
- New Marine Actinobacteria Strain,Microorganisms · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Hyper-porous encapsulation of microbes for whole cell biocatalysis and biomanufacturing.Microbial cell factories · 2025Article
- Tandem mass spectral metabolic profiling of 54 actinobacterial strains and their 459 mutants.Scientific data · 2024Article
- Actinomycetes are a natural resource for sustainable pest control and safeguarding agriculture.Archives of microbiology · 2024Review
- Application of Cas12j forBiomolecules · 2024Article
- Cost-effective hybrid long-short read assembly delineates alternative GC-richSynthetic and systems biotechnology · 2023Article
- Enhancing armeniaspirols production through multi-level engineering of a native Streptomyces producer.Microbial cell factories · 2023Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature's chemical repertoire.
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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.