Antibiotic Discovery Breakthrough: Pre-methylenomycin C lactone Targets Drug-Resistant Bacteria Like MRSA and VRE
- Oct 28
- 2 min read
The global struggle against Antimicrobial Resistance (AMR) has been defined by scarcity and limited innovation, with the World Health Organization (WHO) reporting "too few antibacterials in the pipeline". The crisis is urgent, claiming 1.1 million victims annually. However, a promising new Antibiotic Discovery from chemists at the University of Warwick and Monash University suggests that some of our most powerful weapons may have been right under our noses.
Researchers have identified a potent new antibiotic, pre-methylenomycin C lactone, that was literally "hiding in plain sight". This compound is not entirely new to science but was overlooked because it is an intermediate chemical in the natural process that produces the much older, well-known antibiotic methylenomycin A.
Co-lead author Professor Greg Challis explained that while methylenomycin A was first discovered 50 years ago, no one had previously tested its synthetic intermediates for antimicrobial activity. By deleting biosynthetic genes, the researchers discovered two previously unknown intermediates, both of which proved to be significantly more potent than methylenomycin A itself.
The most impressive finding centered on pre-methylenomycin C lactone. When tested, it demonstrated activity over 100 times more potent against diverse Gram-positive bacteria than the original methylenomycin A. Critically, this activity extends to major Drug-Resistant Bacteria, including S. aureus (the species behind MRSA) and E. faecium (the species behind VRE, or Vancomycin-resistant Enterococcus).
The breakthrough is especially encouraging concerning VRE, which the WHO lists as a High Priority Pathogen. The research team observed that Enterococcus bacteria did not develop resistance to pre-methylenomycin C lactone under laboratory conditions that typically trigger resistance to vancomycin—a treatment considered the "last line" of defense.
A truly surprising element of this Antibiotic Discovery is that the compound is produced by Streptomyces coelicolor, a model antibiotic-producing bacterium that has been extensively studied since the 1950s. Dr. Lona Alkhalaf noted that finding a new antibiotic in such a familiar organism was a "real surprise," suggesting that S. coelicolor might have initially evolved to produce the powerful pre-methylenomycin C lactone before changing it into the weaker methylenomycin A over time.
Professor Challis believes this successful identification of an intermediate suggests a "new paradigm for antibiotic discovery". Instead of relying solely on entirely novel compounds, chemists can now systematically identify and test intermediates in the production pathways of known natural compounds, potentially uncovering potent new antibiotics with better resilience against resistance.
The development path for pre-methylenomycin C lactone appears promising. It possesses a simple structure, potent activity, a "difficult to resist profile," and, crucially, a scalable synthesis route has already been reported in the Journal of Organic Chemistry. The next step for this candidate in the fight against Drug-Resistant Bacteria is pre-clinical testing.
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