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Promiscuous Catalytic Activity Possessed by Novel Enzyme Structure

Nature is a seemingly endless storehouse of interesting ?and potentially life-saving ?biological molecules. But tracking down and harvesting those chemicals in their natural form can be time-consuming, expensive and unreliable.

Now Salk scientists have discovered a new way of bringing “bio-prospecting?out of the rainforest and into the lab. Their findings are published in the June 16th edition of the journal Nature.

Stéphane Richard, Joseph Noel and Tomohisa Kuzuyama isolated and examined a totally new enzyme that can mix and match biological chemicals to create a wide range of different molecules that could be used as the basis for new drugs. The enzyme, named Orf2, takes chemical building blocks known as small aromatic molecules and changes them by adding a fat-like molecule called a prenyl group. That modification can have a huge impact on where the aromatic molecule goes within the cell, and what sort of effects it has when it reaches its target.

“When you make that so-called hybrid molecule, all the chemistry associated with the original compound changes,?said Noel. He explained that the addition of a prenyl group, also known as prenylation, produces a relatively large change in the chemical’s biological properties. “The molecule becomes a little bit more greasy, and so the kinds of targets that it might interact with change completely.?/p>

“We actually have in our hands now the ability to do things that a chemist might not be able to do, or if a chemist was able to do it, it could be expensive and time-consuming,?said Noel. “I think it’s a completely novel way to approach the whole area of bio-prospecting and new natural medicines.?/p>

The group was interested in manipulating the properties of small aromatic molecules because these bacteria- and plant-derived compounds are involved in a wide variety of important biological processes. Some are potent cancer-fighting anti-oxidants, while others have antibiotic or anti-fungal proper
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Source:Salk


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