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Cloning techniques produce FDA-approved antibiotic

The successful synthesis of an antibiotic in a non-native host has provided a team of researchers at the University of Illinois at Urbana-Champaign with the potential for developing new treatments for bacterial infections.

The rapid rise of antibiotic resistance poses a serious threat to human health, and demands new treatments effective against resistant pathogens. Fosfomycin is a natural antibiotic approved by the Food and Drug Administration for the treatment of various bacterial infections, and has proven effective for the treatment of infections that have become resistant to the antibiotics penicillin and vancomycin.

Fosfomycin is a member of a class of compounds called phosphonic acids because they contain a carbon-phosphorous bond. Fosfomycin functions by inactivating an essential enzyme involved in the formation of the bacterial cell wall.

"Phosphonic acids are underexploited bioactive compounds with great potential for treating human disease," said Huimin Zhao, a U. of I. professor of chemical and biomolecular engineering. "We hope to understand the complete pathway for how fosfomycin is made."

In a paper to appear in the Nov. 27 journal Chemistry and Biology, Zhao and U. of I. chemistry professor Wilfred A. van der Donk report the first successful synthesis of fosfomycin in a non-native host.

Fosfomycin is produced by various species of bacteria, but generally in low yields. Using a cloning method developed by Illinois microbiologist William W. Metcalf, the researchers were able to clone the essential genes for fosfomycin synthesis and then produce it in a non-native host, potentially in much larger quantities.

After isolating the genetic information from fosfomycin's native host, Streptomyces fradiae, certain genes were inactivated, and the ability of a non-native host Streptomyces lividians to produce fosfomycin was assessed.

With the help of graduate students Ryan Woodyer and Zengyi Shao, Zhao
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Source:University of Illinois at Urbana-Champaign


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