Microbes to help develop antibiotics

Microbes to help develop antibiotics
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Highlights

Solving a decades-old mystery, researchers, including an Indian-origin scientist, have discovered how a powerful antibiotic agent is made in nature.

Solving a decades-old mystery, researchers, including an Indian-origin scientist, have discovered how a powerful antibiotic agent is made in nature.

This finding has opened up new avenues of research into thousands of similar molecules, many of which are likely to be medically useful. The team focused on a class of compounds that includes dozens with antibiotic properties.

The most famous of these is nisin, a natural product in milk that can be synthesised in the lab and is added to foods as a preservative.

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.

"Peptides are a little bit like spaghetti; they are too flexible to do their jobs," said, University of Illinois chemistry professor, Wilfred van der Donk, who led the research along with biochemistry professor Satish K Nair.

"So what nature does is, it starts putting knobs in, or starts making the peptide cyclical," van der Donk added.

Special enzymes help in the task. For nisin, an enzyme called a dehydratase removes water to help give the antibiotic its final, three-dimensional shape.

This is the first step in converting the spaghetti-like peptide into a five-ringed structure, the researchers noted.

The rings are essential to nisin's antibiotic function: Two of them disrupt the construction of bacterial cell walls, while the other three punch holes in bacterial membranes.

This dual action is very effective, making it difficult for microbes to evolve resistance to the antibiotic, the findings showed.

"It turns out that in nature, a fairly large number of natural products - many of them with therapeutic potential - are made in a similar fashion," van der Donk concluded.

The study appeared in the journal Nature.

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