Aerobic Enzymes and Their Radical SAM Enzyme Counterparts in Tetrapyrrole Pathways

Microorganisms have lifestyles and metabolism adapted to environmental niches, which can be very broad or highly restricted. Molecular oxygen (O₂) is currently variably present in microenvironments and has driven adaptation and microbial differentiation over the course of evolution on Earth. Obligate anaerobes use enzymes and cofactors susceptible to low levels of O₂ and are restricted to O₂-free environments, whereas aerobes typically take advantage of O₂ as a reactant in many biochemical pathways and may require O₂ for essential biochemical reactions. In this Perspective, we focus on analogous enzymes found in tetrapyrrole biosynthesis, modification, and degradation that are catalyzed by O₂-sensitive radical S-adenosylmethionine (SAM) enzymes and by O₂-dependent metalloenzymes. We showcase four transformations for which aerobic organisms use O₂ as a cosubstrate but anaerobic organisms do not. These reactions include oxidative decarboxylation, methyl and methylene oxidation, ring formation, and ring cleavage. Furthermore, we highlight biochemically uncharacterized enzymes implicated in reactions that resemble those catalyzed by the parallel aerobic and anaerobic enzymes. Intriguingly, several of these reactions require insertion of an oxygen atom into the substrate, which in aerobic enzymes is facilitated by activation of O₂ but in anaerobic organisms requires an alternative mechanism.