ArticleACS chemical biology2019
Bioactivity-HiTES Unveils Cryptic Antibiotics Encoded in Actinomycete Bacteria.
Article in ACS chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- When context matters: community and environmental context to elicit natural products.Essays in biochemistry · 2026Review
- Advances in natural product discovery: strategies, technologies, and insights.Natural products and bioprospecting · 2026Review
- Microbial secondary metabolites: advancements to accelerate discovery towards application.Nature reviews. Microbiology · 2025Review
- Crystal Structure, Modeling, and Identification of Key Residues Provide Insights into the Mechanism of the Key Toxoflavin Biosynthesis Protein ToxD.Biochemistry · 2025Article
- Structural and functional analysis of SAM-dependent N-methyltransferases involved in ovoselenol and ovothiol biosynthesis.Structure (London, England : 1993) · 2025Article
- Assessing Normandy Soil Microbial Diversity for Antibacterial Activities Using Traditional Culture and iChip Methods.Microorganisms · 2024Article
- Hirocidins, Cytotoxic Metabolites from Streptomyces hiroshimensis, Induce Mitochondrion-Mediated Apoptosis.Angewandte Chemie (International ed. in English) · 2024Article
- Biotechnological potential of actinomycetes in the 21st century: a brief review.Antonie van Leeuwenhoek · 2024Review
- Discovery and engineering of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products.RSC chemical biology · 2024Review
- Manipulation and epigenetic control of silent biosynthetic pathways in actinobacteria.World journal of microbiology & biotechnology · 2024Review
- Harnessing regulatory networks in Actinobacteria for natural product discovery.Journal of industrial microbiology & biotechnology · 2024Review
- Small molecule inducers of actinobacteria natural product biosynthesis.Journal of industrial microbiology & biotechnology · 2023Review
- Fighting antibiotic resistance-strategies and (pre)clinical developments to find new antibacterials.EMBO reports · 2023Review
- Enhancing chemical and biological diversity by co-cultivation.Frontiers in microbiology · 2023Review
- Bioinformatic prediction and experimental validation of RiPP recognition elements.Methods in enzymology · 2023Article
- Recent Approaches for Downplaying Antibiotic Resistance: Molecular Mechanisms.BioMed research international · 2023Review
- Targeted Discovery of Cryptic Metabolites with Antiproliferative Activity.ACS chemical biology · 2022Article
- Momomycin, an Antiproliferative Cryptic Metabolite from the Oxytetracycline Producer Streptomyces rimosus.Angewandte Chemie (International ed. in English) · 2022Article
- Vitamin B3 Triggers Biosynthesis of Secondary Metabolite Dormancy Signals inJournal of the American Chemical Society · 2022Article
- Induction of Diverse Cryptic Fungal Metabolites by Steroids and Channel Blockers.Angewandte Chemie (International ed. in English) · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Bacteria harbor an immense reservoir of potentially new and therapeutic small molecules in the form of "silent" biosynthetic gene clusters (BGCs). These BGCs can be identified bioinformatically but are sparingly expressed under normal laboratory growth conditions, or not at all, and therefore do not produce significant levels of the corresponding small molecule product. Several methods have been developed for activating silent BGCs. A major limitation for nearly all methods is that they require genetic procedures and/or do not report on the bioactivity of the cryptic metabolite. We herein report "Bioactivty-HiTES", an approach that links the bioactivity of cryptic metabolites to their induction while at the same time obviating the need for genetic manipulations. Using this method, we detected induction of cryptic antibiotics in three actinomycete strains that were tested. Follow-up studies in one case allowed us to structurally elucidate two cryptic metabolites, elicited by the β-blocker atenolol in Streptomyces hiroshimensis, with selective growth-inhibitory activity against Gram-negative bacteria, notably Escherichia coli and Acinetobacter baumannii. Atenolol turned out to be a global elicitor of secondary metabolism, and characterization of additional cryptic metabolites led to the discovery of a novel naphthoquinone epoxide. Bioactivity-HiTES is a general, widely applicable procedure that will be useful in identifying cryptic bioactive metabolites in the future.
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