D. Small Molecules (O2) Activation

D-02 Ribonucleotide reductases—essential radical enzymes Britt-Marie Sjöberg Department of Molecular Biology and Functional Genomics, Stockholm University, 10691 Stockholm, Sweden. britt-marie.sjoberg@molbio.su.se Ribonucleotide reductases (RNRs) catalyse the reduction of ribonucleotides to their corresponding deoxyribonucleotides, providing the sole biological means for de novo synthesis of the building blocks of DNA. Ribonucleotide reduction has evolved only once during evolution and all RNRs make use of a common thiyl radical-based mechanism for catalysis. The three currently known classes of RNR each operate under a distinct set of biochemical and environmental conditions [1]. Class I RNRs contain a diiron center that via oxygenmediated oxidation generates a protein-based tyrosyl radical that is a prerequisite to catalysis. Class II enzymes generate a radical via cleavage of vitamin B12 coenzyme (5 0-deoxyadenosylcobalamin). Class III enzymes generate via S-adenosylmethionine cleavage (by action of an activase protein) a stable protein-based glycyl radical that is sensitive to oxygen. These differences form the basis for the classification of RNRs and result in distinct operational constraints (anaerobicity, iron/oxygen dependence and cobalamin dependence). While the propensity to synthesise deoxyribonucleotides is an essential function, the operational differences suggest that the type(s) of RNR(s) present in an organism will have an impact on the environmental conditions in which it can grow and reproduce. The effect of environmental parameters such as iron, cobalt and oxygen availability on the biochemistry of ribonucleotide reduction will impact our understanding of the adaptability of microorganisms to a range of environments.