Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Promiscuous catalytic activity possessed by novel enzyme structure

17.06.2005


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."

"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."

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 properties. Many of these molecules only become active once they have had a prenyl group added.

The researchers tested whether their new enzyme could modify a wide range of small aromatic molecules, ranging from plant flavonoids - for instance, compounds found in hops that give beer its bitter taste or in other plants act as sunscreens, pigments, or antibiotics - to olivetol, a component in the production of THC, the active ingredient of marijuana. Unlike other previously known prenylation enzymes that only act on a small number of molecules, this new enzyme was able to attach prenyl groups to most of the different aromatic compounds tested. Some of the newly-formed hybrid molecules had previously been found in natural sources, but the enzyme also built some new compounds that had never been seen before.

The key to Orf2’s flexibility seems to reside in the active site, the region of the enzyme where the small aromatic molecules bind. In many enzymes, the structure of the active site only allows one specific molecule to interact with it, like a key fitting into a lock. But the scientists found that Orf2’s active site is a surprisingly spacious barrel-like structure, unlike any protein fold ever seen before. Not only does this wide barrel allow Orf2 to act on such a wide range of aromatic molecules, its discovery could also shed new light on the relationship between an enzyme’s structure, the way it has evolved, and the chemical reactions it is able to carry out.

Although the researchers have not yet had a chance to test the modified molecules to see if their function has changed, they believe that Orf2 could be a powerful tool for creating biologically active compounds that could be used as drugs or as new methods of enhancing the disease-preventative properties of plants. Because the enzyme is able to modify such a wide range of compounds, scientists seeking to develop new drugs could use it in several different ways. If they had no particular end product in mind, they could feed interesting compounds to the enzyme and see what comes out. But researchers could also turn Orf2 into a more customized tool by using the techniques of genetic engineering to narrow its activity and tell it exactly which reactions to carry out.

"The big advantage that we have with our system is that it’s a small, soluble, easy-to-work-with bacterial protein that seems to be able to do reactions that you can find somewhere else in nature, but where people have not been able yet to isolate the proteins," said Stéphane Richard. "So it’s kind of a short-cut - it’s a way to bypass what is done already in nature, but for which we don’t have the tools yet that nature has."

Cathy Yarbrough | EurekAlert!
Further information:
http://www.salk.edu

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>