A new tetronomycin analog, broad‐spectrum and potent antibiotic against drug‐resistant Gram‐positive bacteria

We discovered a new tetronomycin analog, C‐32‐OH tetronomycin (2) from the Streptomyces sp. K20‐0247 strain, which produces tetronomycin (1). After NMR analysis of 2, we determined the planar structure. Futhermore, the absolute stereochemistry of 2 was deduced based on the biosynthetic pathway of 1...

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Bibliographic Details
Published in:Chemistry & biodiversity 2024-02, Vol.21 (2), p.e202301834-n/a
Main Authors: Kimishima, Aoi, Tsuruoka, Iori, Tsutsumi, Hayama, Honsho, Masako, Honma, Sota, Matsui, Hidehito, Sugamata, Miho, Wasuwanich, Paul, Inahashi, Yuki, Hanaki, Hideaki, Asami, Yukihiro
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Antibacterial activity
antibiotic
Antibiotics
antimicrobial resistance (AMR)
Circular dichroism
clinical isolates
Dichroism
Drug resistance
Ethers
Gram-Positive Bacteria
Ionophores
Microbial Sensitivity Tests
natural product
Natural products
NMR
Nuclear magnetic resonance
Planar structures
Stereochemistry
tetronomycin
Vancomycin
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Summary:We discovered a new tetronomycin analog, C‐32‐OH tetronomycin (2) from the Streptomyces sp. K20‐0247 strain, which produces tetronomycin (1). After NMR analysis of 2, we determined the planar structure. Futhermore, the absolute stereochemistry of 2 was deduced based on the biosynthetic pathway of 1 in the K20‐0247 strain and a comparison of experimental electronic circular dichroism (ECD) results of 1 with 2. While 2 exihibits potent antibacterial activity aganist Gram‐positive baceria including vancomycin‐intermediate Staphylococcus aureus (VISA) strains and vancomycin‐resistant Enterococci (VRE), the antibacterial activity of 2 shows 16–32‐folds weaker than that of 1 suggesting that the C‐34 methyl group in 1 is one of the very important functinal group. Moreover, we evaluated the ionophore activity of 1 and 2 and neither compound shows ionophore activity at reasonable concetrations. Our research suggests that 1 and 2 would have different target(s) from an ionophore mechanism in the antibacterial activity and tetronomycins are promising natural products for broad‐spectrum antibiotics.
ISSN:1612-1872
1612-1880
DOI:10.1002/cbdv.202301834