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Molecular level discovery could play role in development of new antibiotics

CHAMPAIGN, Ill. -- Chemists at the University of Illinois at Urbana-Champaign have uncovered the molecular activity of an enzyme responsible for naturally turning a small protein into a potent antibiotic known as a lantibiotic.

The finding is described in the Jan. 30 issue of the journal Science. The research details how the enzyme performs two biosynthetic reactions that lead to the formation of fused cyclic structures required for antimicrobial activity. The discovery unlocks a door that could lead to a new line of antibiotic compounds based on nature's machinery, said Wilfred A. van der Donk, a professor of chemistry at Illinois.

The work was done using lacticin 481, a lantibiotic produced by one of several strains of Lactococcus lactis, a bacterium used in cheese production. Other lantibiotics are used to preserve other dairy products and canned vegetables. The lantibiotic nisin has been used for more than 50 years as an alternative to chemicals in food preservation in more than 40 countries without the development of significant antibiotic resistance.

"The use of antibiotics is an important area of medicine, because pathogenic bacteria are always in the environment," van der Donk said. "It's important to renew our arsenal of compounds that combat pathogens. With the development of resistance -- not just the kind that occurs through evolution but also the kind potentially created in biological weapons by terrorists -- we will always need new antibiotics."

The breakthrough in van der Donk's lab came in March 2003, when his doctoral student Lili Xie, now at the Harvard Medical School, noticed catalytic activity in the material she was investigating. Van der Donk had been pursuing such activity for six years. Many other labs have tried since the late 1980s, when the genes involved in nisin's biosynthetic pathway were sequenced, but efforts to make analogs in vitro had failed.

Lantibiotics are ribosomally synthesized a
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Contact: Jim Barlow, Life Sciences Editor
jebarlow@staff.uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
29-Jan-2004


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