NERD grant of DKK 16 million to Erik Donovan Hedegård from Department of Physics, Chemistry and Pharmacy

Antibiotic resistance is one of the world's most pressing health challenges, as an increasing number of bacteria are becoming resistant to existing treatments. Now, Associate Professor Erik Donovan Hedegård has received a NERD grant from the Novo Nordisk Foundation for a project that could provide researchers with new tools in the fight against resistant bacteria.

“Multidrug-resistant bacteria are a growing global health threat, and developing new antibiotics is becoming increasingly difficult. Our ambition is to contribute to the development of new treatments for resistant bacterial infections,” says Erik Donovan Hedegård.

The project focuses on a newly discovered class of copper-containing enzymes that could have the potential to revolutionise antibiotic production. Before that potential can be realised, however, researchers must first understand the chemical mechanisms that drive the enzymes’ activity.

Nature’s chemical machinery

Enzymes act as nature’s catalysts, enabling chemical reactions to take place rapidly and efficiently in living organisms. A special group of enzymes, known as metalloenzymes, contains metal atoms such as copper, iron, or zinc at their active sites.

These metals allow enzymes to perform some of the most sophisticated chemical transformations found in nature.

Metalloenzymes are therefore essential to processes ranging from photosynthesis to the production of biologically active molecules. Yet predicting their reactivity remains notoriously difficult.

Challenges existing models

Quantum chemical modelling has transformed many areas of scientific research by enabling researchers to predict chemical processes with remarkable accuracy. However, when it comes to metalloenzymes, current models often fall short.

The newly discovered class of copper enzymes pushes existing quantum chemical methods beyond their limits. Their chemistry is so complex that researchers sometimes refer to them as “torture tracks” when attempting to describe their behaviour using conventional computational models.

As a result, scientists are faced with a biological discovery of enormous promise, but without the theoretical tools needed to explain exactly how these enzymes function.

New tools for designing antibiotics

With the new grant, Erik Donovan Hedegård will develop a new generation of quantum chemical models specifically designed to handle metalloenzymes.

The goal is to create theoretical tools capable of revealing how these copper enzymes carry out their chemistry and, at the same time, identify opportunities to translate that knowledge into the development of new antibiotic compounds.

In the longer term, the project could also provide deeper insight into some of nature’s most advanced catalysts, opening new possibilities in biotechnology, drug discovery, and pharmaceutical development.

Project title: A physically rigorous and super fast computational model for metalloenzymes.