Uncovering the Evolutionary Origins of Glycopeptide Antibiotics: A Pathway to Future Antibiotics

A study published in Nature Communications outlines how reconstructing the genetic pathways to create an ancient molecule known as "paleomycin” led researchers to discover that all glycopeptide antibiotics come from a common precursor.  

Researchers utilized advanced bioinformatics to decode the chemical blueprint of ancient glycopeptide antibiotics, aiming to gain insights into their evolutionary trajectory to guide the development of future antibiotics for medical purposes. 

The researchers used glycopeptide antibiotics, including teicoplanin and vancomycin, to disrupt bacterial cell wall construction and cause bacterial death. Numerous human pathogens are susceptible to teicoplanin and vancomycin’s destructive properties. They also discovered a potential ancestral form of these antibiotics called "paleomycin" and successfully synthesized the compound, which showed antibiotic properties in tests. 

The energy-intensive nature of these complex antibiotics poses a benefit for the bacteria that produce them, but streamlining their composition without losing effectiveness could provide an evolutionary advantage. By meticulously studying the evolution of these antibiotics and their genetic sequences, researchers were able to identify the crucial steps necessary for creating functional molecules. This knowledge enabled them to replicate some of these steps in a laboratory setting.  

“This journey through time revealed profound insights into the evolution of bacterial antibiotic pathways and nature's optimization strategies, leading to modern glycopeptide antibiotics,” says Ziemert. “This provides us with a solid foundation for advancing this crucial antibiotic group using biotechnology.” 

Reference 

Kokkoliadis L. Taking antibiotics back in time. EurekAlert! Published online November 30, 2023. https://www.eurekalert.org/news-releases/1009672. Accessed December 04, 2023.