ArticleNature communications2017
The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 84 citations in OpenAlex.
- A genome-wide CRISPR knockout screen identified host genes essential for Brucella invasion and intracellular survival.Emerging microbes & infections · 2026Article
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Article
- Development of Potent and Selective Inhibitors of Methylenetetrahydrofolate Dehydrogenase 2 for Targeting Acute Myeloid Leukemia: SAR, Structural Insights, and Biological Characterization.Journal of medicinal chemistry · 2024Article
- Selectivity analysis of diaminopyrimidine-based inhibitors of MTHFD1, MTHFD2 and MTHFD2L.Scientific reports · 2024Article
- In Situ Biofilm Affinity-Based Protein Profiling Identifies the Streptococcal Hydrolase GbpB as the Target of a Carolacton-Inspired Chemical Probe.Journal of the American Chemical Society · 2024Article
- Nickel-Catalyzed Four-Component Carbonylation of 1,3-Butadiene To Access β,γ-Unsaturated Ketones.Organic letters · 2024Article
- Cycling back to folate metabolism in cancer.Nature cancer · 2024Review
- MTHFD2 in healthy and cancer cells: Canonical and non-canonical functions.npj metabolic health and disease · 2024Review
- MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.Cell death & disease · 2024Article
- Targeting one-carbon metabolism for cancer immunotherapy.Clinical and translational medicine · 2024Review
- Targeting allosteric binding site in methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to identify natural product inhibitors via structure-based computational approach.Scientific reports · 2023Article
- Direct allylic acylation via cross-coupling involving cooperative N‑heterocyclic carbene, hydrogen atom transfer, and photoredox catalysis.Nature communications · 2023Article
- Targeting serine-glycine-one-carbon metabolism as a vulnerability in cancers.Biomarker research · 2023Review
- Article
- Review
- Discovery of Myeloid-Derived Suppressor Cell-Specific Metabolism by Metabolomic and Lipidomic Profiling.Metabolites · 2023Article
- Metabolomics in oncology.Cancer reports (Hoboken, N.J.) · 2023Review
- A bacterial pan-genome makes gene essentiality strain-dependent and evolvable.Nature microbiology · 2022Article
- Deacetylation of MTHFD2 by SIRT4 senses stress signal to inhibit cancer cell growth by remodeling folate metabolism.Journal of molecular cell biology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The natural product carolacton is a macrolide keto-carboxylic acid produced by the myxobacterium Sorangium cellulosum, and was originally described as an antibacterial compound. Here we show that carolacton targets FolD, a key enzyme from the folate-dependent C1 metabolism. We characterize the interaction between bacterial FolD and carolacton biophysically, structurally and biochemically. Carolacton binds FolD with nanomolar affinity, and the crystal structure of the FolD-carolacton complex reveals the mode of binding. We show that the human FolD orthologs, MTHFD1 and MTHFD2, are also inhibited in the low nM range, and that micromolar concentrations of carolacton inhibit the growth of cancer cell lines. As mitochondrial MTHFD2 is known to be upregulated in cancer cells, it may be possible to use carolacton as an inhibitor tool compound to assess MTHFD2 as an anti-cancer target.
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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.