With illumination, biochemists turn on and off DNA functions

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To pass photocaging groups to DNA, biochemists use protein engineering.

Life on earth is based on DNA (deoxyribonucleic acid).

DNA’s function is to store all the genetic data that an organism requires to grow, function and reproduce.

It is basically a manual for biological guidance that can be found in every cell.

With the aid of light, biochemists at the University of Münster have now developed a technique to monitor the biological functions of DNA.

This helps researchers to better understand and monitor the different processes taking place in the cell, such as epigenetics, the critical chemical transition, and the DNA control lever.

The findings were published in Angewandte Chemie, a journal.

Context and methodology
Special molecules called enzymes rely on cellular functions.

Proteins that carry out chemical reactions in the cell are enzymes.

They help to synthesize metabolites, make copies of DNA molecules, transform energy for the activities of the cell, alter DNA epigenetically, and degrade those molecules.

A research team led by Prof.

A so-called enzymatic cascade reaction was used by Andrea Rentmeister from the Institute of Biochemistry at the University of Münster to better understand and follow these functions.

This sequence of successive reaction steps involving various enzymes enables the transfer to DNA of so-called photocaging groups – chemical groups which can be extracted by light irradiation. Previous studies have shown that only small residues (small alterations like methyl groups) can be passed to DNA, RNA (ribonucleic acid) or proteins very selectively.

Nils Klöcker, one of the lead study authors and a doctoral student at the Institute of Biochemistry, explains: “Through our work, it is now possible to also transfer larger residues or modifications such as the photocaging groups just mentioned,”

Together with the structural biologist, Prof.

The basis of the altered behavior at the molecular level could also be clarified by Daniel Kümmel, who also works at the Institute of Biochemistry.

The Münster researchers redesigned an enzyme in the cascade using so-called protein engineering – a technique for which a Nobel Prize was awarded in 2018 – so that it can turn DNA functions on and off with the aid of light.

The design of the protein allowed them to extend the enzymes’ substrate spectrum – in this case, methionine adenosyltransferase (MATs).

The researchers studied two MATs in their work.

The improvements made provide a starting point for the creation of an extended substrate variety of other MATs.

For future cellular applications, mixing these MATs with other enzymes has potential.

In epigenetic studies, this is a significant move towards the use of in situ produced non-natural compounds for other enzymes, says Andrea Rentmeister.

‘Engineered SAM Synthetases for Enzymatic Generation of AdoMet Analogs in Cascade Reactions with Photocaging Groups and Reversible DNA Modification’ by Dr.

Nils Klöcker, Freideriki Michailidou, Nicolas V.

Cornelissen, Dr. Rohit K. Singh, Anna Ovcharenko, Aileen Peters, Prof. Dr.

Other professors include Daniel Kümmel and Prof. Dr.

Applied Chemistry, Andrea Rentmeister, Oct. 5, 2020. DOI: 10.1002/anie.202012623.
Funding: The German Research Foundation (DFG), the European Research Council (ERC) and the IRTG Münster-Toronto network have financially sponsored the report.

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