Antimicrobial Agents & Resistance

Synthetic Versions of Teixobactin Kill Superbugs as Well as the Natural Form

 

Researchers at the University of Lincoln in the UK have created two synthetic versions of teixobactin that kill superbugs, from MRSA to tuberculosis, as well as the natural form of the antibiotic and take only 10 minutes to produce.

Team leader Ishwar Singh explained that, until now, people attempting to synthesize teixobactin thought they had to reproduce enduracididine, a very rare amino acid in the drug that everyone thought was essential to its potency.  Enduracididine is a cationic (positively charged) amino acid that binds to the bacterial target with a side chain.  There is no way to create a synthetic version of it at the current time, so researchers were using other cationic amino acids with side chain binders to take its place.  Unfortunately, these substitutions reduced the potency to unacceptable levels.

The Lincoln team finally tried amino acids that were not positively charged and lack binding capacity and they worked, proving that target binding is not essential to antibacterial potency.

“This simplified design and more efficient synthesis will enable work to be carried out at a commercial level,” said Singh.  “Enduracididine was severely limiting our ability to do this because of its scarcity, a complex multistep synthesis [process], and long and repetitive [synthetic] steps of between 16 and 30 hours with high failure rates and very low yields…Now we have discovered that we can, in fact, use amino acids that are structurally different and commercially available.  They are also 16 times more potent than a [currently] used antibiotic in killing the superbug MRSA…and other antibiotic-resistant infections.”

For more information, go to Chemical Science at pubs.rsc.org/-/content/articlehtml/2017/cc/c7cc04021k.

 

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