Radical Enzymes

Abstract

Radical 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 B 12 , S ‐adenosylmethionine (SAM), or dioxygen with bi‐transition metal centers. Coenzyme B 12 ‐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 B 12 ‐ 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.

A physiological perspective on the origin and evolution of photosynthesis

“…4 might occur—whether it entails one electron to two electron-transducing cofactors such as a flavin or quinone, or whether it might involve sulfur radicals. There are many thiyl radicals in biology (Buckel and Golding 2006 ), including thiyl to tyrosyl transfers as in the reaction mechanism of ribonucleotide reductase (Buckel and Golding 2012 ). However, the first step in H 2 S oxidation to sulfur or polysulfide is typically a two-electron reaction (Luther 2010 ; Luther et al.…”

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

“…Experimentally it has been shown that 1 (2). A higher energy barrier has been calculated for reaction with adenine, giving for the first time an explanation of the lack of reactivity of 1 O 2 toward adenine.…”

“…Radical enzymes catalyze reactions in which species with an odd number of electrons, classically described as "free radicals", participate [2]. This area has been intensively developed in recent decades and is now a major sub-discipline of enzymology.…”

Substrate-Induced Radical Formation in 4-Hydroxybutyryl Coenzyme A Dehydratase from Clostridium aminobutyricum

“…The radicalgenerating system consists of Y296, FAD, and [4Fe-4S], whereby the initially formed FAD· Ϫ gets a proton from the water channel via E257 and T190. This system is quite different from those of other anaerobic enzymes, which use coenzyme B 12 , Sadenosylmethionine (radical SAM enzymes), ATP-driven electron transfer, or flavin-based electron bifurcation (6,14,65). The formation of FADH· in 4HBD ensures a one-electron oxidation of the substrate, which is necessary to form the allylic ketyl radical that eliminates the hydroxyl group.…”