Journal of the American Chemical Society (JACS)
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Journal of the American Chemical Society (JACS)
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Research, news, and information from the Journal of the American Chemical Society: pubs.acs.org/JACS
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Reposted by Journal of the American Chemical Society (JACS)
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Chemists discovered a powerful hidden antibiotic that’s 100 times stronger than existing ones and effective against deadly superbugs.

The study has been published in the Journal of the American Chemical Society. YES, it is PEER-REVIEWED.
• pubs.acs.org/doi/10.1021/...

🧪🧵⬇️
Summary A team of scientists discovered a hidden antibiotic 100 times stronger than existing drugs against deadly superbugs like MRSA. The molecule had been overlooked for decades in a familiar bacterium. It shows no signs of resistance so far, offering hope in the fight against drug-resistant infections and paving the way for new approaches to antibiotic discovery. Abstract The methylenomycins are highly functionalized cyclopentanone antibiotics produced by Streptomyces coelicolor A3(2). A biosynthetic pathway to the methylenomycins has been proposed based on sequence analysis of the proteins encoded by the methylenomycin biosynthetic gene cluster and the incorporation of labeled precursors. However, the roles played by putative biosynthetic enzymes remain experimentally uninvestigated. Here, the biosynthetic functions of enzymes encoded by mmyD, mmyO, mmyF, and mmyE were investigated by creating in-frame deletions in each gene and investigating the effect on methylenomycin production. No methylenomycin-related metabolites were produced by the mmyD mutant, consistent with the proposed role of MmyD in an early biosynthetic step. The production of methylenomycin A, but not methylenomycin C, was abolished in the mmyF and mmy mutants, consistent with the corresponding enzymes catalyzing the epoxidation of methylenomycin C, as previously proposed. Expression of mmyF and mmyo in a S. coelicolor M145 derivative engineered to express mmr, which confers methylenomycin resistance, enabled the resulting strain to convert methylenomycin C to methylenomycin A, confirming this hypothesis. A novel metabolite (premethylenomycin C), which readily cyclizes to form the corresponding butanolide (premethylenomycin C lactone), accumulated in the mmyE mutant, indicating the corresponding enzyme is involved in introducing the exomethylene group into methylenomycin C. Remarkably, both premethylenomycin C and its lactone precursor were one to two orders of magnitude more active against various Gram-positive bacteria, including antibiotic-resistant Staphylococcus aureus and Enterococcus faecium isolates, than methylenomycins A and C, providing a promising starting point for the development of novel antibiotics to combat antimicrobial resistance. Graphical Abstract
November 16, 2025 at 7:32 PM
jacs.acspublications.org
Great work, Brandon! ✨
October 29, 2025 at 10:17 AM