Discovery paves the way for new synthesis of antibiotics
March 5, 2012
Lori Ann White
“Researchers working at SLAC have used powerful X-rays to help decipher how certain natural antibiotics defy a longstanding set of chemical rules – a mechanism that has baffled organic chemists for decades.
Their result, reported today in Nature, details how five carbon atoms and one oxygen atom in the structure of lasalocid, a natural antibiotic produced by bacteria in soil, can link into a six-membered ring through an energetically unfavorable chemical reaction. Unlocking this chemical pathway could enable scientists to synthesize many important chemicals currently found only in nature.
‘Our study has a broad implication because the six-membered ring is a common structural feature found in hundreds of drug molecules produced by nature,’ said the study’s principal investigator, Chu-Young Kim of the National University of Singapore. ‘We have actually analyzed the genes of six other organisms that produce similar drugs and we are now confident that the chemical mechanism we have uncovered applies to these other organisms as well.’
A ribbon diagram of the protein Lsd19, which catalyzes the formation of six-membered rings in lasalocid. Image by Kinya Hotta
To determine the protein’s atomic structure, the researchers hit frozen crystals of Lsd19 with X-rays from SLAC’s Stanford Synchrotron Radiation Lightsource and observed how the crystals diffracted the X-rays passing through. ‘You need atomic-level detail of the crystal’s structure to understand what’s really happening,” said co-author Irimpan Mathews, a staff scientist at SLAC.”
See the full article here.
SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science. 
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