Biochemists turn DNA functions on and off using light

Biochemists use protein engineering to transfer groups of DNA.

DNA (deoxyribonucleic 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 basically a biological instruction manual found in every cell.

Biochemists at the University of Münster have now developed a strategy to control the biological functions of DNA using light. This allows researchers to better understand and control the different processes that take place in the cell – for example epigenetics, key chemical change, and DNA regulatory lever.

The results were published in the journal applied chemistry.

Context and methodology

The functions of the cell depend on special molecules, enzymes. Enzymes are proteins that perform chemical reactions in the cell. They help synthesize metabolic products, make copies of DNA molecules, convert energy for cell activities, epigenetically modify DNA, and break down certain molecules.

A team of researchers led by Professor Andrea Rentmeister of the Institute of Biochemistry at the University of Münster used an enzymatic cascade reaction to better understand and track these functions. This sequence of successive reaction steps involving different enzymes makes it possible to transfer so-called photocaging groups – chemical groups, to DNA, which can be removed by irradiation with light. Previously, studies had shown that only small residues (small changes such as methyl groups) could be very selectively transferred to DNA, RNA (ribonucleic acid) or proteins.

“Thanks to our work, it is now possible to transfer larger residues or modifications such as the photocaging groups just mentioned”, explains Nils Klöcker, one of the main authors of the study and doctoral student at Institute of Biochemistry. Together with the structural biologist, Professor Daniel Kümmel, who also works at the Institute of Biochemistry, it was also possible to explain the basis of the change in activity at the molecular level.

Using what is known as protein engineering – a method for which a Nobel Prize was awarded in 2018 – researchers in Münster designed an enzyme in the cascade, which turns the functions of the cell on and off. DNA by means of light. Using protein design, it has been possible to broaden the spectrum of enzyme substrates – in this case, methionine adenosyltransferases (MAT). In their work, the researchers examined two MATs. The modifications made offer a starting point for the development of other MAT with a broad spectrum of substrates.

“The combination of these MAT with other enzymes has potential for future cellular applications. This is an important step for the implementation of unnatural substances generated in situ for other enzymes in epigenetic studies ”, says Andrea Rentmeister.

Reference: “SAM Synthetases Designed for Enzymatic Generation of AdoMet Analogues with Photocaging Clusters and Reversible DNA Modification in Cascade Reactions” by Dr. Freideriki Michailidou, Nils Klöcker, Nicolas V. Cornelissen, Dr. Rohit K. Singh, Aileen Peters, Anna Ovcharenko, Prof. Dr. Daniel Kümmel and Prof. Dr. Andrea Rentmeister, October 5, 2020, applied chemistry.
DOI: 10.1002 / anie.202012623

Funding: The study received financial support from the German Research Foundation (DFG), the European Research Council (ERC) and the “IRTG Münster-Toronto” network.