Characterization of a novel natural tetracenomycin reveals crucial role of 4-hydroxy group in ribosome binding
The aromatic polyketides tetracenomycins were recently found to be potent inhibitors of protein synthesis. Their binding site is located in a unique locus within the tunnel of the large ribosomal subunit. Here we report the isolation and structure elucidation of a novel natural tetracenomycin congener - O-Me-tetracenomycin C (O-Me-TcmC). This compound is isomeric to tetracenomycin X (TcmX), however, in contrast to TcmX, O-Me-TcmC exhibited no antimicrobial activity and was unable to inhibit protein synthesis in vitro. Structural alignment of tetracenomycins to the binding locus from cryo-EM TcmX-70S ribosome data revealed the crucial role of the 4-hydroxyl group. These findings are important for further development of semi-synthetic tetracenomycins as potential antibacterials.
![](/images/pubmed.gif)
Список научных проектов, где отмечена публикация
- Development of means of prevention and treatment of COVID-19 and concomitant infectious diseases using genetic technologies (September 28, 2021 December 31, 2023). . Agreement / contract, Ministry of Science.