Researchers from the universities of Warwick, in the United Kingdom, and Monash, in Australia, discovered pre-methylenemycin C lactone, a compound up to 100 times more potent than conventional antibiotics against resistant bacteria. The molecule, produced by Streptomyces coelicolor, acts effectively against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). The identification occurred during an analysis of intermediates in the production of methylenemycin A, published in the Journal of the American Chemical Society on October 27, 2025.
The substance demonstrated a minimum inhibitory concentration of 1 to 2 micrograms per milliliter in laboratory tests.
- Effective against Gram-positive bacteria with thick cell walls.
- No development of resistance after 28 days of exposure.
- Simple structure facilitates artificial synthesis.
Origin in known biosynthetic pathway
Scientists have genetically manipulated Streptomyces coelicolor to stop the production of methylenemycin A.
They deactivated the mmyE gene, responsible for the final transformation of the intermediate.
The accumulation of pre-methylenemycin C lactone revealed its superior potency.
The bacterium has been a study model since the 1950s.
Chemical structure favors antimicrobial action
The molecule belongs to the lactone family, with a functionalized cyclopentanone ring.
A γ-butyrolactone group acts as the active center, destabilizing the bacterial cell wall.
Epoxidation inserts oxygen into the epoxide ring, increasing reactivity.
This configuration differentiates the compound from the original methylenemycin A.
Tests highlight low concentration required
In experiments, the lactone inhibited the growth of Gram-positive bacteria with minimal doses.
Traditional antibiotics require concentrations tens of times higher.
Chemical stability allows creation of analogues to optimize efficacy.
Results indicate potential against serious infections in hospital environments.
Crisis of resistance drives research
Antimicrobial resistance caused 1.14 million direct deaths in 2021, according to global data.
One in every six bacterial infections confirmed in 2023 was antibiotic resistantcommon cos.
The increase was more than 40% in pathogen-antibiotic combinations between 2018 and 2023.
Factors include excessive use in humans and animals.
Strategy revisits old compounds
Researchers propose examining intermediates in known biosynthetic pathways.
The approach could reveal new antimicrobial agents.
Preclinical tests in animal models evaluate safety and efficacy.
Laboratory synthesis enables scaled production.
Potential against hospital pathogens
The lactone combats MRSA and VRE, responsible for difficult-to-treat infections.
Gram-negative bacteria remain challenging due to the double cell wall.
The compound focuses on Gram-positives, complementing existing therapeutic options.
Teams prepare modifications to reduce adverse effects.
