As the global health threat of antimicrobial resistance (AMR) continues to rise, scientists have uncovered a promising new antibiotic that could aid in the fight against drug-resistant bacteria.
According to a recent study published in the Journal of the American Chemical Society (JACS), researchers from the Monash Warwick Alliance's Combatting Emerging Superbug Threats Initiative have identified a compound called pre-methylenomycin C lactone, previously overlooked in antibiotic research.
This newly discovered molecule was found as an intermediate step in the natural production of methylenomycin A, a well-known antibiotic. Researchers described the find as a breakthrough "hiding in plain sight," suggesting it may have been missed in earlier studies because it was not the final product of the biosynthetic pathway.
The discovery comes amid growing concern from the World Health Organisation (WHO), which recently warned of an urgent lack of new antibiotics in development. With the most easily accessible antibiotics already discovered, and low commercial incentives discouraging pharmaceutical investment, new findings like this one are critical.
"Methylenomycin A was originally discovered 50 years ago and while it has been synthesised several times, no-one appears to have tested the synthetic intermediates for antimicrobial activity! By deleting biosynthetic genes, we discovered two previously unknown biosynthetic intermediates, both of which are much more potent antibiotics than methylenomycin A itself," Co-lead author of the study, Professor Greg Challis, in the Department of Chemistry at the University of Warwick, and Biomedicine Discovery Institute at Monash University said in a statement.
Co-lead author Dr Lona Alkhalaf, Assistant Professor, University of Warwick adds: "Remarkably, the bacterium that makes methylenomycin A and pre-methylenomycin C lactone, Streptomyces coelicolor, is a model antibiotic-producing species that's been studied extensively since the 1950s. Finding a new antibiotic in such a familiar organism was a real surprise."
"It looks like S coelicolor originally evolved to produce a powerful antibiotic (pre-methylenomycin C lactone), but over time has changed it into methylenomycin A - a much weaker antibiotic that may play a different role in the bacterium's biology."
The identification of pre-methylenomycin C lactone not only opens new avenues for antibiotic development but also highlights the importance of re-examining known pathways and intermediates for overlooked therapeutic potential.
