ArticleProceedings of the National Academy of Sciences of the United States of America2011
Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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137 citing papers in PubMed, 314 citations in OpenAlex.
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- Molecular biology and integrated strategies for activating cryptic biosynthetic gene clusters toward next-generation antibiotic discovery.Frontiers in bioinformatics · 2026Review
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- Genome mining based on transcriptional regulatory networks uncovers a novel locus involved in desferrioxamine biosynthesis.PLoS biology · 2025Article
- Genome Mining Reveals Rifamycin Biosynthesis in a Taklamakan Desert Actinomycete.Microorganisms · 2025Article
- Exploring the Synthetic Potential of Horner-Wadsworth-Emmons Reaction Toward the Synthesis of Polyketide Based Natural Products: A Review.Topics in current chemistry (Cham) · 2025Review
- A new cannabigerolic acid derivative and its unprenylated precursor produced through the reconstitution of cannabinoid biosynthesis in Streptomyces.The Journal of antibiotics · 2025Article
- Diosgenin producingComputational and structural biotechnology journal · 2025Article
- Transcriptional regulators of secondary metabolite biosynthesis in Streptomyces.World journal of microbiology & biotechnology · 2024Review
- Effect of Precursors and Their Regulators on the Biosynthesis of Antibiotics inMolecules (Basel, Switzerland) · 2024Review
- Discovery of thiazostatin D/E using UPLC-HR-MS2-based metabolomics and σ-factor engineering ofFrontiers in bioengineering and biotechnology · 2024Article
- Genomic insights into an endophyticFrontiers in microbiology · 2024Article
- Mukaiyama aldol reaction: an effective asymmetric approach to access chiral natural products and their derivatives/analogues.RSC advances · 2023Review
- New Insights on Biological Activities, Chemical Compositions, and Classifications of Marine Actinomycetes Antifouling Agents.Microorganisms · 2023Review
- An efficient method for targeted cloning of large DNA fragments from Streptomyces.Applied microbiology and biotechnology · 2023Article
- Recent advances in the direct cloning of large natural product biosynthetic gene clusters.Engineering microbiology · 2023Review
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7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is a constant need for new and improved drugs to combat infectious diseases, cancer, and other major life-threatening conditions. The recent development of genomics-guided approaches for novel natural product discovery has stimulated renewed interest in the search for natural product-based drugs. Genome sequence analysis of Streptomyces ambofaciens ATCC23877 has revealed numerous secondary metabolite biosynthetic gene clusters, including a giant type I modular polyketide synthase (PKS) gene cluster, which is composed of 25 genes (nine of which encode PKSs) and spans almost 150 kb, making it one of the largest polyketide biosynthetic gene clusters described to date. The metabolic product(s) of this gene cluster are unknown, and transcriptional analyses showed that it is not expressed under laboratory growth conditions. The constitutive expression of a regulatory gene within the cluster, encoding a protein that is similar to Large ATP binding of the LuxR (LAL) family proteins, triggered the expression of the biosynthetic genes. This led to the identification of four 51-membered glycosylated macrolides, named stambomycins A-D as metabolic products of the gene cluster. The structures of these compounds imply several interesting biosynthetic features, including incorporation of unusual extender units into the polyketide chain and in trans hydroxylation of the growing polyketide chain to provide the hydroxyl group for macrolide formation. Interestingly, the stambomycins possess promising antiproliferative activity against human cancer cell lines. Database searches identify genes encoding LAL regulators within numerous cryptic biosynthetic gene clusters in actinomycete genomes, suggesting that constitutive expression of such pathway-specific activators represents a powerful approach for novel bioactive natural product discovery.
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