ArticleScientific reports2021
Eliciting the silent lucensomycin biosynthetic pathway in Streptomyces cyanogenus S136 via manipulation of the global regulatory gene adpA.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 29 citations in OpenAlex.
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- Emerging synthetic biology-assisted technologies for overcoming antibiotic resistance: CRISPR-Cas, bacteriophage, microbiome, and metabolic engineering-based solutions.Journal of microbiology (Seoul, Korea) · 2026Review
- Identification of antifungal metabolites from a soil-derived Streptomyces strain active against Fusarium graminearum using genome mining.Biotechnology letters · 2025Article
- Complete Genome Assembly ofGenes · 2024Article
- Rapid spectrophotometric detection for optimized production of landomycins and characterization of their therapeutic potential.Biotechnology and bioengineering · 2024Article
- Transcriptional regulators of secondary metabolite biosynthesis in Streptomyces.World journal of microbiology & biotechnology · 2024Review
- Isolation of Streptomyces inhibiting multiple-phytopathogenic fungi and characterization of lucensomycin biosynthetic gene cluster.Scientific reports · 2024Article
- The Impact of Heterologous Regulatory Genes from Lipodepsipeptide Biosynthetic Gene Clusters on the Production of Teicoplanin and A40926.Antibiotics (Basel, Switzerland) · 2024Article
- Discovery of thiazostatin D/E using UPLC-HR-MS2-based metabolomics and σ-factor engineering ofFrontiers in bioengineering and biotechnology · 2024Article
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- Integrated Metabolomic-Genomic Workflows Accelerate Microbial Natural Product Discovery.Analytical chemistry · 2022Review
- ActinoBase: tools and protocols for researchers working onMicrobial genomics · 2022Article
- New Glycosylated Polyene Macrolides: Refining the Ore from Genome Mining.Antibiotics (Basel, Switzerland) · 2022Review
- Fungal Endophytes: A Potential Source of Antibacterial Compounds.Journal of fungi (Basel, Switzerland) · 2022Review
- Genetic approaches to improve clorobiocin production in Streptomyces roseochromogenes NRRL 3504.Applied microbiology and biotechnology · 2022Article
- Genome Sequence-Guided Finding of Lucensomycin Production byMicroorganisms · 2021Article
- AdpA Positively Regulates Morphological Differentiation and Chloramphenicol Biosynthesis in Streptomyces venezuelae.Microbiology spectrum · 2021Article
- Complete genome sequence of3 Biotech · 2021Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Actinobacteria are among the most prolific sources of medically and agriculturally important compounds, derived from their biosynthetic gene clusters (BGCs) for specialized (secondary) pathways of metabolism. Genomics witnesses that the majority of actinobacterial BGCs are silent, most likely due to their low or zero transcription. Much effort is put into the search for approaches towards activation of silent BGCs, as this is believed to revitalize the discovery of novel natural products. We hypothesized that the global transcriptional factor AdpA, due to its highly degenerate operator sequence, could be used to upregulate the expression of silent BGCs. Using Streptomyces cyanogenus S136 as a test case, we showed that plasmids expressing either full-length adpA or its DNA-binding domain led to significant changes in the metabolome. These were evident as changes in the accumulation of colored compounds, bioactivity, as well as the emergence of a new pattern of secondary metabolites as revealed by HPLC-ESI-mass spectrometry. We further focused on the most abundant secondary metabolite and identified it as the polyene antibiotic lucensomycin. Finally, we uncovered the entire gene cluster for lucensomycin biosynthesis (lcm), that remained elusive for five decades until now, and outlined an evidence-based scenario for its adpA-mediated activation.
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