Investigation of a novel group of small ribonucleotide reductases

Ribonucleotide reductase (RNR) is essential for life as the only known enzyme that can produce deoxyribonucleotides, the building blocks required for DNA repair and duplication.

Depending on their environment organisms use different classes of RNR, whose activity is mostly dependent on the presence or absence of oxygen and the availability of different metal cofactors.

RNRs are therefore an important target for the development of cancer treatments and new antibiotics. 50-years of research focused on three classes until recently a new group was described based on genes found in genome-wide databases, proposed to represent a fourth class of RNRs.

The newly discovered proteins are distinctly smaller than known proteins and appear evolutionary closer to an ancestral RNR from which the other three classes developed. The goal of my project is to characterize this new group of RNR.

I want to I) show activity, II) investigate the regulation of the protein and, III) define the minimal requirements of a working RNR based on the new group over three years at TU Dortmund and Stockholm University.

Comparing the results will define this group in relation to known classes, illuminate the catalytic mechanism and allow us to conclude if it indeed represents a new class of RNRs.

Functional characterization of a minimal RNR will provide central information regarding both fundamental biochemical requirements for ribonucleotide reduction and understanding of how modern RNRs evolved.