A natural depsipeptide antibiotic binds the E-site of the bacterial ribosome

Manikomycin, a novel natural depsipeptide antibiotic, binds to the E-site of the bacterial large ribosomal subunit, as detailed in a study published online on June 3, 2026, in Nature. This discovery, stemming from improved fractionation strategies, highlights the potential for identifying antibiotics with previously unseen scaffolds and mechanisms of action. Manikomycin is produced by the bacterium Streptomyces rimosus. The research demonstrates that targeting the E-site offers a new avenue for antibiotic development, potentially overcoming existing resistance mechanisms. The identification of manikomycin underscores the importance of exploring diverse microbial sources for novel antimicrobial compounds. This finding could lead to the development of new therapeutic agents to combat bacterial infections, a growing global health concern.