Radical Enzymes

AbstractRadical enzymes catalyze reactions with intermediate radicals, which are not free but bound to the enzyme. The catalytic reactions comprise generation of a radical species that initiates formation of the substrate‐derived radical, followed by conversion to the product‐related radical, and either recycling or decomposition of the initiating radical with release of the product. These characteristics are illustrated with specific radical enzymes. Ribonucleotide reductases (RNRs) use a thiyl radical to enable a common reaction mechanism for the reduction of ribose. There are three classes of RNRs that differ in the manner of thiyl radical generation: use of coenzyme B12,S‐adenosylmethionine (SAM), or dioxygen with bi‐transition metal centers. Coenzyme B12‐dependent eliminases and mutases are like SAM radical enzymes in that they apply the same 5′‐deoxyadenosyl radical as initiating radical, which is also used by coenzyme B12‐ or SAM‐dependent RNRs. The SAM radical enzymes, which multiply in number, are involved in the maturation of enzymes and transfer of ribonucleic acids, as well as in the biosynthesis of many vitamins, coenzymes, and antibiotics. The 2‐ and 4‐hydroxyacyl‐coenzyme A (CoA) dehydratases contain a [4Fe–4S] cluster and utilize intermediate ketyl radicals, which are formed either by reduction or by combined oxidation/deprotonation of the substrates. Similar radical species participate in the reduction of benzoyl‐CoA and other aromatic compounds as well as in photolyases that repair DNA. Finally, flavin radical enzymes and two [4Fe–4S] cluster enzymes of the nonmevalonate pathway of isoprenoid biosynthesis are described. In conclusion, biotechnological applications and evolutionary aspects are discussed.