ABSTRACTAdenine has long been recognized for its critical roles in cellular metabolism and the storage of genetic information. However, the mechanism by which ATP, derived from adenine, outperforms nucleotides formed from other nucleobases as the primary energy currency remains unclear. In this study, we demonstrate that metabolism of all nucleobases produces hydrogen peroxide (H2O2), which serves as a key substrate for extracellular Fenton chemistry, a cellular energy mechanism that facilitates the increase of environmental temperature and the degradation of organic matter. Among the nucleobases, adenine metabolism generates the highest H2O2 levels, followed by guanine. Using thermophilic fungi as a model, we found that compared with the mutant without the extracellular Fenton reactions, wild‐type strains with the extracellular Fenton chemistry showed downregulation of NTP synthesis and upregulation of nucleoside triphosphate degradation, resulting in H2O2 production. The function of nucleosides as crucial reserves for the extracellular Fenton reactions of organisms may offer insights into potential and natural functions of stop codons, poly(A) tails in RNA biosynthesis, junk DNA
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