Biochemists use protein engineering to transfer photos into caching groups DNA.
DNA (deoxyrib on nucleic) Acid) Is the basis of life on earth. The function of DNA is to store all the genetic information that an organism needs to grow, function and reproduce. It is essentially the biological instruction found in every cell.
Biochemists at Monster University Now a strategy has been developed to control the biological functions of DNA with the help of light. This enables researchers to better understand and control the various processes that take place in a cell – for example epigenetics, key chemical mutations and regular liver transplantation in DNA.
The results have been published in the journal Engandte Chemi.
Background and method
The functions of the cell are based on special molecules, enzymes. Enzymes are proteins that carry out chemical processes in cells. They help in the synthesis of metabolic products, replication of DNA molecules, conversion of energy to cell activity, altering DNA epigenetically and breaking down certain molecules.
A team of researchers led by Prof. Andrea Rentmeister from the Institute of Biochemistry at the University of Monster used the so-called enzymatic cascade reaction to better understand and track these functions. This sequence of sequential reaction steps involving various enzymes makes it possible to transfer so-called photosynthetic groups – chemical groups, which can be removed by irradiation with light – into DNA. Previously, studies have shown that only small residues (small mutations such as methyl groups) can be very selectively transferred into DNA, RNA (Ribuc nucleic acid) or protein.
“As a result of our work, it has become possible to transfer large fossils or alterations, such as the now-registered photocajing groups,” explains Nils Klucker, lead author of the study and a PhD student in biochemistry. Structural Biologist Prof. Daniel Camel, who also works in biochemistry, working together, was also able to explain the basis of altered activity at the molecular level.
Using so-called protein engineering – a method for which the Nobel Prize was awarded in 2018 – Monster researchers engineered an enzyme in a cascade that made it possible to turn DNA function on and off through light. With the help of protein design, it was possible to expand the substrate spectrum of enzymes – in this case, methionine adenosyltransferases (MATS). In their work, researchers examined two MATs. The changes made provide a starting point for developing other MATs with extended substrate spectrum.
“The combination of this matte with other enzymes has the potential for future cellular application. This is an important step for other enzymes in epigenetic studies to apply natural and non-natural substances produced in the situation, ”says Andrea Rentmeister.
Reference: “Engineered SAM Synthetics and Reverse Receivable DNA Improvement in Cascade Reactions for Enzymatic Generation of Adolescent Analogs with Photocajing Groups” by Dr. Frey Friedrich Michalido, Nils Clöcker, Nicholas V. Prof. Dr. Daniel Camel and Prof. D And. Re October 2020, Andrea Rentmister, Engandte Chemi.
DOI: 10.1002 / anie.202012623
Funding: The study was funded by the German Research Foundation (DFG), the European Research Council (ERC) and the IRTG Münster-Toronto Network.