ArticlemBio2016
Strain Prioritization and Genome Mining for Enediyne Natural Products.
Article in mBio, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed.
- A Dual-Functional Magnetic Nanoparticle for Rapid Extraction and Targeted Tumor Delivery of Tiancimycin.Molecules (Basel, Switzerland) · 2026Article
- Article
- Discovery of phenoxazine congeners as novel α-glucosidase inhibitors and identification of their biosynthetic gene cluster from Streptomyces sp. CB00316.Archives of microbiology · 2025Article
- A conserved terpene cyclase gene in Sanghuangporus for abscisic acid-related sesquiterpenoid biosynthesis.BMC genomics · 2025Article
- A guide to genome mining and genetic manipulation of biosynthetic gene clusters in Streptomyces.Journal of microbiology (Seoul, Korea) · 2025Article
- Advances in the Study of Halogenated Natural Products.Current topics in medicinal chemistry · 2025Review
- The exploration of high production of tiancimycins in Streptomyces sp. CB03234-S revealed potential influences of universal stress proteins on secondary metabolisms of streptomycetes.Microbial cell factories · 2024Article
- Combined transcriptomic and pangenomic analyses guide metabolic amelioration to enhance tiancimycins production.Applied microbiology and biotechnology · 2024Article
- Genomic Comparisons Revealed the Key Genotypes ofBioengineering (Basel, Switzerland) · 2024Article
- Enediyne natural product biosynthesis unified by a diiodotetrayne intermediate.Nature chemical biology · 2024Article
- Article
- Genome mining for new enediyne antibiotics.Current opinion in chemical biology · 2024Review
- Enantioselective Synthesis of Sealutomicin C.Journal of the American Chemical Society · 2024Article
- Anti-HER2 Immunoliposomes: Antitumor Efficacy Attributable to Targeted Delivery of Anthraquinone-Fused Enediyne.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Biochemical and Structural Studies of the Carminomycin 4-Journal of natural products · 2024Article
- Cofactorless oxygenases guide anthraquinone-fused enediyne biosynthesis.Nature chemical biology · 2024Article
- The Impact of Heterologous Regulatory Genes from Lipodepsipeptide Biosynthetic Gene Clusters on the Production of Teicoplanin and A40926.Antibiotics (Basel, Switzerland) · 2024Article
- Targeted Discovery of Cryptic Enediyne Natural Products via FRET-Coupled High-Throughput Elicitor Screening.ACS chemical biology · 2023Article
- Normal and Aberrant Methyltransferase Activities Give Insights into the Final Steps of Dynemicin A Biosynthesis.Journal of the American Chemical Society · 2023Article
- Prioritization of Microorganisms Isolated from the Indian Ocean SpongeMicroorganisms · 2023Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors.
Funding
Abstract
The enediyne family of natural products has had a profound impact on modern chemistry, biology, and medicine, and yet only 11 enediynes have been structurally characterized to date. Here we report a genome survey of 3,400 actinomycetes, identifying 81 strains that harbor genes encoding the enediyne polyketide synthase cassettes that could be grouped into 28 distinct clades based on phylogenetic analysis. Genome sequencing of 31 representative strains confirmed that each clade harbors a distinct enediyne biosynthetic gene cluster. A genome neighborhood network allows prediction of new structural features and biosynthetic insights that could be exploited for enediyne discovery. We confirmed one clade as new C-1027 producers, with a significantly higher C-1027 titer than the original producer, and discovered a new family of enediyne natural products, the tiancimycins (TNMs), that exhibit potent cytotoxicity against a broad spectrum of cancer cell lines. Our results demonstrate the feasibility of rapid discovery of new enediynes from a large strain collection. IMPORTANCE: Recent advances in microbial genomics clearly revealed that the biosynthetic potential of soil actinomycetes to produce enediynes is underappreciated. A great challenge is to develop innovative methods to discover new enediynes and produce them in sufficient quantities for chemical, biological, and clinical investigations. This work demonstrated the feasibility of rapid discovery of new enediynes from a large strain collection. The new C-1027 producers, with a significantly higher C-1027 titer than the original producer, will impact the practical supply of this important drug lead. The TNMs, with their extremely potent cytotoxicity against various cancer cells and their rapid and complete cancer cell killing characteristics, in comparison with the payloads used in FDA-approved antibody-drug conjugates (ADCs), are poised to be exploited as payload candidates for the next generation of anticancer ADCs. Follow-up studies on the other identified hits promise the discovery of new enediynes, radically expanding the chemical space for the enediyne family.
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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.