PUBLICATION
Erythromycin Stress Upregulates Antiangiogenic Metabolites in the Gut Bacterium Aneurinibacillus aneurinilyticus
- Authors
- Ha, Y.J., Hwang, S.J., Hong, S., Kim, J., Kim, M., Lee, G.S., Lee, S.H., Kim, H., Lee, B.S., In An, H., Kim, K.H., Lee, W., Lee, H.J., Kim, C.S.
- ID
- ZDB-PUB-250501-4
- Date
- 2025
- Source
- Journal of the American Chemical Society : (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Up-Regulation*/drug effects
- Human Umbilical Vein Endothelial Cells/drug effects
- Erythromycin*/chemistry
- Erythromycin*/pharmacology
- Angiogenesis Inhibitors*/chemistry
- Angiogenesis Inhibitors*/metabolism
- Angiogenesis Inhibitors*/pharmacology
- Anti-Bacterial Agents*/pharmacology
- Mice
- Humans
- Gastrointestinal Microbiome*/drug effects
- Zebrafish
- PubMed
- 40305844 Full text @ J. Am. Chem. Soc.
Citation
Ha, Y.J., Hwang, S.J., Hong, S., Kim, J., Kim, M., Lee, G.S., Lee, S.H., Kim, H., Lee, B.S., In An, H., Kim, K.H., Lee, W., Lee, H.J., Kim, C.S. (2025) Erythromycin Stress Upregulates Antiangiogenic Metabolites in the Gut Bacterium Aneurinibacillus aneurinilyticus. Journal of the American Chemical Society. :.
Abstract
The interplay among antibiotics, gut microbiota, and disease pathogenesis remains poorly understood, particularly in the context of rare gut bacteria. This study identifies a novel correlation between erythromycin-induced stress and the production of antiangiogenic metabolites in Aneurinibacillus aneurinilyticus, a human gut bacterium. We report the isolation and structural characterization of aneuristatin (1), a metabolite featuring a unique pyrrolo[1,2-a]pyrazine scaffold, along with seven structurally related metabolites (2-8) from A. aneurinilyticus ATCC 12856T. These metabolites were upregulated via the erythromycin-induced activation of the arnA biosynthetic gene. Aneuristatin (1) enhanced prolyl hydroxylase activity, promoting hypoxia-inducible factor-1α (HIF-1α) degradation and reducing downstream targets, including VEGF and EPO. It also exhibited antioxidant effects by reducing ROS levels under hypoxia. Additionally, it inhibited angiogenesis in HUVECs and zebrafish and effectively reduced inflammation, fibrosis, and angiogenesis in a mouse corneal injury model. Our study establishes a molecular basis for the potential of erythromycin-induced aneuristatin (1) to prevent or treat angiogenesis-related diseases such as cancer.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping