Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Birth Of An Enzyme

25.03.2008
Scientists succeed in designing artificial enzymes that also undergo 'evolution in a test tube'

A team of scientists from the University of Washington, Seattle, and the Weizmann Institute of Science, Israel, has succeeded in creating a new type of enzyme for a reaction for which no naturally occurring enzyme has evolved, by using a combination of novel computational methodologies and molecular in vitro evolution. This achievement opens the door to the development of a variety of potential applications in medicine and industry.

Mankind triumphed in a recent 'competition' against nature when scientists succeeded in creating a new type of enzyme for a reaction for which no naturally occurring enzyme has evolved. This achievement opens the door to the development of a variety of potential applications in medicine and industry.

Enzymes are, without a doubt, a valuable model for understanding the intricate works of nature. These molecular machines - which without them, life would not exist - are responsible for initiating chemical reactions within the body. Millions of years of natural selection have fine-tuned the activity of such enzymes, allowing chemical reactions to take place millions of times faster. In order to create artificial enzymes, a comprehensive understanding of the structure of natural enzymes, their mode of action, as well as advanced protein engineering techniques is needed. A team of scientists from the University of Washington, Seattle, and the Weizmann Institute of Science, Israel, made a crucial breakthrough toward this endeavor. Their findings have recently been published in the scientific journal Nature.

Enzymes are biological catalysts that are made from a string of amino acids, which fold into specific three-dimensional protein structures. The scientists' aim was to create an enzyme for a specific chemical reaction whereby a proton (a positively charged hydrogen atom) is removed from carbon - a highly demanding reaction and rate-determining step in numerous processes for which no enzymes currently exist, but which would be beneficial in helping to speed up the reaction. During the first heat of the 'competition,' the research team designed the 'heart' of the enzymatic machine - the active site - where the chemical reactions take place.

The second heat of the competition was to design the backbone of the enzyme, i.e., to determine the sequence of the 200 amino acids that make up the structure of the protein. This was no easy feat seeing as there is an infinite number of ways to arrange 20 different types of amino acids into strings of 200. But in practice, only a limited number of possibilities are available as the sequence of amino acids determines the structure of the enzyme, which in turn, determines its specific activity. Prof. David Baker of the University of Washington, Seattle, used novel computational methodologies to scan tens of thousands of sequence possibilities, identifying about 60 computationally designed enzymes that had the potential to carry out the intended activity. Of these 60 sequences tested, eight advanced to the next 'round' having showed biological activity. Of these remaining eight, three sequences got through to the 'final stage,' which proved to be the most active. Drs. Orly Dym and Shira Albeck of the Weizmann Institute's Structural Biology Department solved the structure of one of the final contestants, and confirmed that the enzymes created were almost identical to the predicted computational design.

But the efficiency of the new enzymes could not compare to that of naturally-occurring enzymes that have evolved over millions of years. This is where 'mankind' was on the verge of losing the competition to nature, until Prof. Dan Tawfik and research student Olga Khersonsky of the Weizmann Institute's Biological Chemistry Department stepped in, whereby they developed a method allowing the synthetic enzymes to undergo 'evolution in a test tube' that mimics natural evolution. Their method is based on repeated rounds of random mutations followed by scanning the mutant enzymes to find the ones who showed the most improvement in efficiency. These enzymes then underwent further rounds of mutation and screening. Results show that it takes only seven rounds of evolution in a test tube to improve the enzymes' efficiency 200-fold compared with the efficiency of the computer-designed template, resulting in a million-fold increase in reaction rates compared with those that take place in the absence of an enzyme.

The scientists found that the mutations occurring in the area surrounding the enzyme's active site caused minor structural changes, which in turn, resulted in an increased chemical reaction rate. These mutations therefore seem to correct shortcomings in the computational design, by shedding light on what might be lacking in the original designs. Other mutations increased the flexibility of the enzymes, which helped to increase the speed of substrate release from the active site.

'Reproducing the breathtaking performances of natural enzymes is a daunting task, but the combination of computational design and molecular in vitro evolution opens up new horizons in the creation of synthetic enzymes,' says Tawfik. 'Thanks to this research, we have gained a better understanding of the structure of enzymes as well as their mode of action. This, in turn, will allow us to design and create enzymes that nature itself had not 'thought' of, which could be used in various processes, such as neutralizing poisons, developing medicines, as well as for many further potential applications.'

Prof. Dan Tawfik's research is supported by the J & R Center for Scientific Research; the Jack Wolgin Prize for Scientific Excellence; Mr. and Mrs. Yossie Hollander, Israel; Mr. Rowland Schaefer, New York, NY; and the estate of Fannie Sherr, New York, NY. Prof. Tawfik is the incumbent of the Elaine Blond Career Development Chair.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.

Weizmann Institute news releases are posted on the World Wide Web at
http://wis-wander.weizmann.ac.il, and are also available at http://www.eurekalert.org.

Yivsam Azgad | idw
Further information:
http://wis-wander.weizmann.ac.il

Further reports about: Active Computational Efficiency Mutation acids activity amino amino acids determine enzyme reaction

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>