Identification and development of new enzymes

Danh Phuong

The confusing interplay of other proteins and chemicals serves as the basis for most biological activities that require the involvement of enzymes, specialized molecules to increase the chemical reactions between them. molecule.

In the August 16 issue of Nature , two researchers at Massachusetts General Hospital described a method for making strange enzymes that for the first time did not require a precise knowledge of the How enzymes work.

"Until now, the only source of enzymes was biology," said Jack Szostak, lead author of the Department of Molecular Biology at Massachusetts General Hospital . Great efforts are approaching the revision and improvement of these natural enzymes, and our work demonstrates the potential of fully evolving the new enzyme in the laboratory. '

(Artwork: Search) Szostak and his co-author Dr. Burckhard Seelig used a new technique called exposing mRNA - previously developed in Szostak's laboratory - to allow identification and Development of proteins in accordance with specific standards. To create an enzyme that stimulates or catalyzes the junction of two RNA fragments in an unnatural way, they began by creating a library containing 4 trillion small proteins along with negligible changes. in their strings. At that time, each protein carries the fragments of RNA connected together, called the substrate .

If a particular protein stimulates the RNA substrate to connect, resulting in significant results in a larger molecule, making the protein important, it is a true enzyme . The investigator could select larger strands of RNA, produce more enzymes, and repeat the experiment. Stimulation generates random mutations to produce different types of enzymes and reduces the time for coupling reactions, which helps the development of versions more effective by evolving as directed. .

Szostak noted that the final version of the enzyme they had created was too small and still unstable, but that was the starting point for sub-discovery strategies that could improve its performance. Similar mRNA display techniques can also identify enzymes that break or diminish their buffering molecules.

Szostak explains: 'We hope that this work based on this optimistic enzyme will prove that we can develop catalysts that work as well as naturally occurring enzymes. We also want to determine how the new 3D structure of the enzyme binds to a larger buffer and catalytic binding of two RNA strands. "

Szostak is also a professor of Genetics at Harvard Medical School, an investigator at Howard Hughes Medical Institute and a member of the Center for Integrated Biology. The study is supported by a grant from NASA's Space Biology Institute, and Seelig's somewhat supported by Deutsche Forschungsgemeinschaft's Emmy Noether-Programm program.