Laccase-mediated biotransformation potential for fluorinated compounds by geographically diverse human gut microbiota.

The growing prevalence of synthetic organofluorine substances in agrochemicals, food packaging, and consumer products has led to increasing gastrointestinal exposure, with potential consequences for human health. Despite the extreme stability of fluorinated compounds, several microbial pathways for their transformation are known, including those involving laccases, a type of multicopper oxidase. However, the functionality of laccases in the gut microbiome, a natural contact point between food-associated chemicals and microbial biotransformation pathways, is poorly defined. Through a multi-study analysis of 1,578 human gut metagenomes spanning a global gradient from hunter-gatherer societies to industrialized urban populations, we found that laccase-coding gene homologs are widely distributed in the human gut microbiome. We identified a significant association between both the abundance and phylogenetic diversity of laccase homologs and the degree of urbanization. As human gut microbial laccase activity has not been experimentally demonstrated, eight gut metagenome-derived laccases were heterologously expressed and screened for activity with a redox mediator system. Six of the eight laccases demonstrated activity. One of these gut microbial laccases, derived from