Researchers Make Breakthrough Discovery in the Formation of the Powerful Anitbiotic Nisin

Researchers, led by chemistry professor Wilfred Van Der Donk and biochemistry professor Satish K. Nair, at the University of Illinois at Urbana-Champaign have made a breakthrough discovery in understanding how a powerful antibiotic agent is made in nature. The research serves as a breakthrough solving several decades old mystery that opens up new avenues of research for thousands of other molecules most of which are expected to be useful medically.

The research team focused on numerous compounds including those with antibiotic properties. One compound in particular of note was Nisin. Nisin is a natural product found in milk that is used to combat food borne pathogens. Researchers have long been able to understand and assemble the sequence of the nisin gene; however, after it is made the peptide undergoes several modifications which lead to the peptides final formation. Several decades of research have been spent trying to understand how these changes occur.  

Peptides are extremely flexible so in order for them to do their jobs enzymes are put in to make the peptide cyclical. In nisin, a dehydratase removes water which helps give the antibiotic the final desired three-dimensional shape which is the first step in converting the peptide into a five ringed structure. The rings are essential to nisin’s antibiotic function because of their dual action. Specifically, two of the rings disrupt the construction of bacterial cell walls while the other three rings punch holes in the bacterial membrane. The dual action of Nisin makes it much more difficult for microbes to evolve resistance to the antibiotic.

Previous studies have showed that the dehydratase enzyme was involved in the modifications of the Nisin structure. However, no study before this was able to show how the dehydratase made these modifications. Without this understanding it has not been possible to discover and understand similar compounds that may also be useful in fighting food-borne diseases and/or dangerous microbial infections.

The team’s research discovered that that the amino acid glutamate was essential to nisin's transformation. Professor Nair stated, “They discovered that the dehydratase did two things. One is that it added glutamate (to the nisin peptide), and the second thing it did was it eliminated glutamate. But how does one enzyme have two different activities?”

Through X-ray crystallography the team discovered that the dehydratase interacts with the peptide in two different ways: one part of the enzyme grasps the peptide while a separate part helps install the ring structures. The other important discovery the team made was that t-RNA supplies the glutamate which allows the dehydratase to help shape nisin into its final structure.

This research is very important because it signals a breakthrough in an area that for decades has not been understood. I think the discoveries from this research will be the first step in helping other labs make new discoveries that were not possible before. Additionally, this research will lead to fighting both food-borne diseases and dangerous microbial infections more effectively. 

Main Article: http://www.sciencedaily.com/releases/2014/10/141026195415.htm

Secondary Article: http://www.science20.com/news_articles/how_to_build_a_powerful_antibiotic-147727