ArticleChemical science2020
Biosynthesis of the fungal glyceraldehyde-3-phosphate dehydrogenase inhibitor heptelidic acid and mechanism of self-resistance.
Article in Chemical science, 2020. 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, 21 citations in OpenAlex.
- An Antifungal with a Novel Mechanism of Action Discovered via Resistance Gene-Guided Genome Mining.ACS central science · 2026Article
- Is heptelidic (koningic) acid a microbial hormone that regulates secondary metabolism in the biocontrol fungus Trichoderma virens?Current genetics · 2025Article
- Noncanonical terpene cyclases for the biosynthesis of diterpenoids regulating chlamydospore formation in plant-associated Trichoderma.Nature communications · 2025Article
- Plant defense-directed discovery of a natural anti-psoriasis agent targeting GAPDH.Science advances · 2025Article
- Resistance Gene-Guided Genome Mining Reveals RPL10 as the Target of Ligustrone A.Journal of the American Chemical Society · 2025Article
- Chelerythrine Chloride Alleviated Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Glycolytic Pathway Through Targeting Glyceraldehyde-3-Phosphate Dehydrogenase.Molecules (Basel, Switzerland) · 2025Article
- Glyceraldehyde-3-phosphate dehydrogenase/1,3-bisphosphoglycerate-NADH as key determinants in controlling human retinal endothelial cellular functions: Insights from glycolytic screening.The Journal of biological chemistry · 2025Article
- Resistance gene-guided genome mining reveals the roseopurpurins as inhibitors of cyclin-dependent kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Characterization of the depsidone gene cluster reveals etherification, decarboxylation and multiple halogenations as tailoring steps in depsidone assembly.Acta pharmaceutica Sinica. B · 2023Article
- RNA-Seq Based Transcriptome Analysis ofJournal of fungi (Basel, Switzerland) · 2022Article
- Open Search-Based Proteomics Reveals Widespread Tryptophan Modifications Associated with Hypoxia in Lung Cancer.Oxidative medicine and cellular longevity · 2022Article
- COX Inhibitory and Cytotoxic Naphthoketal-Bearing Polyketides fromInternational journal of molecular sciences · 2021Article
- Molecular methods unravel the biosynthetic potential ofRSC advances · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Overcoming resistance to bioactive small molecules is a significant challenge for health care and agriculture. As a result, efforts to uncover the mechanisms of resistance are essential to the development of new antibiotics, anticancer drugs and pesticides. To study how nature evolves resistance to highly potent natural products, we examined the biosynthesis and mechanism of self-resistance of the fungal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor heptelidic acid (HA). HA is a nanomolar inhibitor of GADPH through the covalent modification of the active site cysteine thiol. The biosynthetic pathway of HA was elucidated, which uncovered the enzymatic basis of formation of the epoxide warhead. Structure-activity relationship study using biosynthetic intermediates established the importance of the fused lactone ring system in HA. The molecular basis of HA inhibiting human GAPDH was illustrated through the crystal structure of
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Registered trials
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