It was in the late 1990s that it became apparent that class III RNR functioned with cofactors and chemical mechanisms used by other enzyme systems, such as pyruvate formate lyase, lysine aminomutase and biotin synthase. In fact, the availability of a growing number of sequenced genomes and the use of bioinformatics to analyze them has led to the conclusion of the existence of a very large family of enzymes called " Radical-SAM ", to which these few "historic" systems belong. All the members (several thousand!) of this family have a [4Fe-4S] center attached by 3 cysteines of the "signature" sequence CXXXCXXC, require SAM to function and involve a 5'-deoxyadenosyl radical to activate a substrate, be it a small molecule (such as dethiobiotin or lysine) or a macromolecule (protein such as RNR, DNA or transfer RNA).
All these enzymes also share striking structural similarities. What's remarkable is that the same chemistry is used to carry out a wide variety of chemical transformations, in numerous biosynthetic and metabolic reactions: biosynthesis of cofactors, modification of proteins and nucleic acids, synthesis of antibiotics, synthesis of amino acids and sugars, and so on. In this lecture, the chemical properties of certain members of this family, such as lysine aminomutase or the ThiH enzyme involved in thiamine biosynthesis, are discussed in detail.
