Scientists have solved a decades-old mystery and have made a breakthrough by revealing how a powerful antibiotic agent is made.
The team from University of Illinois focused on a class of compounds that included dozens with antibiotic properties. The most famous of these is nisin, a natural product in milk that could be synthesized in the lab and is added to foods as a preservative. Nisin has been used to combat food-borne pathogens since the late 1960s.
Researchers have long known the sequence of the nisin gene, and they can assemble the chain of amino acids (called a peptide) that are encoded by this gene. But the peptide undergoes several modifications in the cell after it is made, changes that give it its final form and function. Researchers have tried for more than 25 years to understand how these changes occur.
For nisin, an enzyme called a dehydratase removes water to help give the antibiotic its final, three-dimensional shape. This was the first step in converting the spaghetti-like peptide into a five-ringed structure, said lead researcher Wilfred van der Donk.
Professor Satish Nair said that they discovered that the dehydratase did two things. One was to add glutamate (to the nisin peptide), and the second thing was to eliminated glutamate. One enzyme had two different activities, as there was a part of the nisin precursor peptide that was held steady, and there was a part that was flexible. And the flexible part was actually where the chemistry was carried out.
The study is published in the journal Nature.