Understanding microbial mercury methylation via metabolic pathways: Processes associated with one-carbon metabolism

Microbial mercury methylation is the key step responsible for the high toxicity and bioaccumulation potential of mercury. Since metabolic pathways serve as a bridge between mercury methylation and microbial activity, studying mercury methylation from the perspective of metabolic pathways will offer valuable insights into its underlying mechanism and integration into microbial metabolism. This review aims to summarize current understanding of the metabolic pathways that supply methyl groups for mercury methylation and to elucidate the relationships between them. The acetyl-coenzyme A pathway is extensively studied and well recognized for its role in methyl group transfer. The Wolfe cycle, representing the methanogenesis pathway in methanogenic archaea, has recently been identified as a distinct source of methyl groups contributing to mercury methylation. In addition, at the chemical level, S-adenosyl-L-methionine from the methionine biosynthesis pathway has been shown to donate a methyl group to mercury via the HgcAB complex, although this process has not yet been validated in vivo. Finally, the dimethylsulfoniopropionate degradation pathway is proposed as a speculative and potential route for mercury methylation. By integrating these pathways, we provide a comprehensive overview of their interconnections, demonstrating that microbial mercury methylation is embedded within the broader framework of one-carbon metabolism. The close association between methylation and one-carbon flux suggests that mercury methylation may function as an interspecies competition strategy that enhances microbial survival in mercury-rich environments. This pathway-centered perspective advances our understanding of the biochemical basis of microbial mercury methylation and may inform future research into its environmental controls and microbial ecology.