( ose activity we have demonstrated in th...)Creation of antibiotic in test tube holds promise for better antibiotics

The thioether rings vary in size from four to seven amino acids and provide sturdy protease-resistant bonds at precise locations. They account for nisin's robust resistance capability. It was theorized that one enzyme makes all five rings despite their very different sizes, but how it did so was like the mystery of a magic show, van der Donk said.

Nisin is one of numerous members of a family of compounds called lantibiotics, all of which are candidates for bioengineering into new pharmaceuticals, van der Donk said. The key is learning more about the enzymes involved in their biosynthesis. "Our work, while not explaining everything, has brought us much closer to that understanding, in particular the beautiful structure solved by the Nair group," he said.

Van der Donk previously had identified the molecular activity of another enzyme (LctM) responsible for naturally turning a small protein into a lantibiotic. That discovery, reported in Science in 2004, involved lacticin 481.

The new research also showed that NisC has unexpected structural similarities with mammalian farnesyl transferases, which are important for the activity of the RAS protein which when mutated is implicated in 25 percent of breast cancers. Preventing farnesylation possibly could prevent the cancerous effects, because the mutant protein would no longer be localized at the membrane, Nair said.

An accompanying Perspectives article in Science, written by chemist David W. Christianson of the University of Pennsylvania, suggests that nisin's five thioether rings may turn out to be golden "in the never-ending search for blockbuster antibiotics."