Lecture

Radical biological chemistry : from the origin of DNA to today's metabolism

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It is generally accepted that free radicals, highly reactive chemical species, are poisons for living systems, which have developed effective mechanisms to protect themselves from them and to get rid of them when they are formed, by accident. For example, what is commonly known as oxidative stress is a situation characterized by an accumulation of molecular oxygen radicals, such as the superoxide radical or the hydroxyl radical, which exceeds the body's antioxidant capacities. In extreme situations, this can lead to serious pathologies.

This idea of the biological incompatibility of radicals needs to be fundamentally challenged in the light of a whole series of biochemical observations which demonstrate that a very large number of metabolic and biosynthetic reactions involve radical intermediates, remarkably well controlled, opening up the spectrum of chemical possibilities for transforming living matter. This complex chemistry will be illustrated, for example, by the case of ribonucleotide reductases, the enzymes responsible for the biosynthesis of deoxyribonucleotides, the precursors of DNA. Other radical enzymatic systems, belonging to the Radical-S-Adenosyl-Methionine superfamily of enzymes, involved for example in the biosynthesis of sulfur cofactors, vitamins, antibiotics, in the modification of transfer RNAs and proteins, or in DNA repair processes, will be presented.

The presentation of ribonucleotide reductases, which are essential for DNA synthesis, will provide an opportunity to discuss in detail a major issue in the chemical evolution of life, namely the transition from the ancient and now extinct " RNA world " to the current " DNA world ". Indeed, it is commonly accepted that life began with RNA and proteins, and that DNA is a late product of evolution. The role of a primitive ribonucleotide reductase and the importance of viruses in the "invention of DNA" will be discussed in particular.

Program