DNA (deoxyribonucleic acid) is the basis of life on earth. DNA is used to store all the genetic information, which an organism needs to develop, function and reproduce. It plays an important role as a biological instruction manual found in every cell.
In a new research at the University of Münster, biochemists have developed a strategy for controlling the biological functions of DNA with the aid of light. This gives an aid for researchers to understand and control the different processes which take place in the cell. Example: epigenetics, the key chemical change and regulatory lever in DNA.
We know that the cell’s functions depend on special molecules, the enzymes. These are proteins which carry out chemical reactions in the cell. These help in synthesizing metabolic products, make copies of the DNA molecules, convert energy for the cell’s activities, change DNA epigenetically and break down certain molecules.
The team lead by Prof.Andrea Rentmeister from the Institute of Biochemistry at the University of Münster used enzymatic cascade reaction in order to understand and track these functions better. This sequence of successive reaction steps involving different enzymes has made it possible to transfer photocaging groups which are chemical groups which can be removed by irradiation with light — to DNA.
Previous studies only showed that small residues (small modifications such as methyl groups) could be transferred very selectively to DNA, RNA (ribonucleic acid) or proteins. Nils Klöcker, one of the lead authors of the study and a PhD student at the Institute of Biochemistry, explains that their work has enabled them to transfer larger residues or modifications such as the photocaging groups just mentioned. Prof.Daniel Kümmel, who also works at the Institute of Biochemistry, was also in the research told that it was also possible to explain the basis for the changed activity at a molecular level.
The Münster researchers engineered one enzyme in the cascade, making it possible to switch DNA functions on and off by light. It was possible to expand the substrate spectrum of enzymes — in this case, methionine adenosyltransferases (MATs) with the help of protein design. The researchers examined two MATs. Modifications carried out offered a starting point for the development of other MATs with an expanded substrate spectrum. “Combining these MATs with other enzymes has potential for future cellular applications. This is an important step for implementing in situ generated, non-natural substances for other enzymes in epigenetic studies,” says Andrea Rentmeister. The results have been published in the journal Angewandte Chemie.
Freideriki Michailidou, Nils Klöcker, Nicolas V. Cornelissen, Rohit K. Singh, Aileen Peters, Anna Ovcharenko, Daniel Kümmel, Andrea Rentmeister. Maßgeschneiderte SAM‐Synthetasen zur enzymatischen Herstellung von AdoMet‐Analoga mit Photoschutzgruppen und zur reversiblen DNA‐Modifizierung in Kaskadenreaktionen. Angewandte Chemie, 2020; 133 (1): 484 DOI: 10.1002/ange.202012623
Press Release: University of Münster