Next Antibiotic May Come From Dirt Bacteria, Work Funded by Alfred P. Sloan Foundation Finds

Friday, August 2, 2019

Next Antibiotic May Come From Dirt Bacteria, Work Funded by Alfred P. Sloan Foundation Finds

Understanding how antibiotic scaffolds construct in nature can help prospect for new classes of antibiotics through DNA sequencing and genome mining. Scientists used this knowledge to help solve the X-ray crystal structure of the enzyme that makes obafluorin.

A multi-part enzyme called a nonribosomal peptide synthetase produces the highly reactive beta-lactone ring that is responsible for obafluorin’s antimicrobial activity, researchers say.

“Obafluorin has a novel structure compared to all FDA-approved antibiotics,” says Timothy Wencewicz, assistant professor of chemistry at Washington University in St. Louis. “In the long term, we really need new structural classes of antibiotics that have never been contaminated by clinical resistance from established antibiotic classes.”

Scientists could use these chemicals as next-generation antibiotics for humans, or even to benefit the agriculture sector, Wencewicz notes—as researchers strive to engineer seed treatments and biopesticides to support plant systems capable of making enough food to feed the 9.6 billion people projected to live on this planet by 2050.

The new work, published in Nature Communications, provides a useful road map that shows how individual protein domains in the ObiF1 enzyme stitch together in three-dimensional space. An enzyme’s structure is fundamental to almost every function it performs.

“The solution of this structure expands on previous discoveries to provide views of the molecular interactions between catalytic domains in a brand new way,” says Andrew M. Gulick, associate professor in the structural biology department in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo...

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