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Professor Andreas Marx is Professor of Organic Chemistry/Cellular Chemistry at the University of Konstanz, speaker of the Konstanz Graduate School of Chemical Biology, and co-founder of the company myPOLS Biotec, a spin-off of the University of Konstanz for the further development and marketing of application-optimized DNA polymerases. He works at the interface between biology and chemistry, and his primary focus of interest is on targeted synthesis of biomolecules with tailor-made properties and functions, whose application provides insights into complex biological processes.

Deoxyribonucleic acid (DNA) vs. xenonucleic acid (XNA)
In the course of his Reinhart Koselleck project, which has just been granted by the German Research Foundation (DFG), Marx will deepen his research in the field of synthetic genetics, in particular with regard to non-natural genetic polymers, so-called xenonucleic acids (XNAs). It is known that natural nucleic acids such as deoxyribonucleic acid (DNA) are excellent for storing and transmitting information. “DNA stores up to 200 petabytes of information per gram, and it does so with high chemical stability,” according to the scientist. In contrast, other conventional storage media – CDs, tapes, the hard disk of a computer – have rather short life spans.

In synthetic genetics, alternative synthetic nucleic or xenonucleic acids have been studied for some time with a view to storage, transmission and generation of information: “XNA has the same potential as DNA in terms of storing and retrieving information, or folding into functional units. However, xenonucleic acids have the great advantage over their natural counterparts that they are even more stable, by a considerable margin. They are therefore of particular interest for applications such as data storage, biotechnology, or molecular medicine,” explains Marx.

XNA enzymes: “Machines” for reading and writing XNA
The key to the exploration and development of xenonucleic acids lies in certain enzymes that write (XNA polymerases) and read (XNA reverse transcriptases) XNA. Although progress has already been made in the development of such XNA enzymes, the low efficiency and fidelity of the enzymes previously developed with xeno substrates still poses a major challenge. “Obtaining a structural insight into the basics of how XNA enzymes write and read XNA would be of great benefit for synthetic genetics,” says Marx. In the long term, the insights into the chemical boundary conditions of genetic transactions thus gained are expected to enable development of highly efficient XNA enzymes.

In cooperation with experts of worldwide renown, Philip Holliger from the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) in Cambridge, Piet Herdewyn from the Katholieke Universiteit Leuven, and Kay Diederichs at the University of Konstanz, Andreas Marx will in the course of his Koselleck project, for the first time ever, systematically investigate the interactions of XNA polymerases and XNA transcriptases with their substrates with regard to structural aspects. To this end, the teams of scientists will express and purify the enzymes, synthesise corresponding substrates, and then image and evaluate them by means of crystallization.

With the Koselleck project, the scientists hope to close a knowledge gap in the long term, and tap into new fields of application in medicine and biotechnology. “At present it is not yet possible to predict whether we will even find suitable conditions for the crystallization of these artificial systems,” Marx comments on his research project, which from a scientific point of view is risky in a positive sense. “However, due to our pioneering work on the interaction of DNA polymerases and unnatural substrates already done at the University of Konstanz, I am very optimistic.”

About the Reinhart Koselleck Projects of the German Research Foundation (DFG)
Reinhart Koselleck Projects enable scientists who have made a name for themselves through their outstanding scientific achievements to carry out research that is particularly innovative and risky in a positive sense. The funding period is typically five years, with a funding amount between 500,000 and 1.25 million euros.

Andreas Marx will receive funding from the German Research Foundation (DFG) for his project to the amount of one million euros plus a programme allowance of 220,000 euros. Funding is expected to start in November 2020.

Key facts:

• Konstanz-based chemist Professor Andreas Marx, working at the Department of Chemistry at the University of Konstanz, has been awarded a Reinhart Koselleck project from the German Research Foundation (DFG) for his work in the field of synthetic genetics.
• Research into the structural principles of writing and reading synthetic genetic polymers, so-called xenonucleic acids (XNAs).
• Collaboration with scientists in the field of xenonucleic acids from Cambridge and Leuven.
• Potential areas of application include biotechnology and long-term data storage, as well as molecular medicine.
• Funding amount: One million euros plus 220,000 euros programme allowance.
• Start of funding: Presumably November 2020.
• Funding period: Five years.