Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
Paola Nol Bernadino
Department of Chemistry and Molecular Biology, University of California, Irvine, Irvine, United States; Department of Chemistry and Molecular Biochemistry, University of California, Irvine, Irvine, United States
Michael U Luescher
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
Sina Kiamehr
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
Chip Le
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States; Chan Zuckerberg Biohub, San Francisco, United States
Department of Chemistry and Molecular Biology, University of California, Irvine, Irvine, United States; Department of Chemistry and Molecular Biochemistry, University of California, Irvine, Irvine, United States
Catechol dehydroxylation is a central chemical transformation in the gut microbial metabolism of plant- and host-derived small molecules. However, the molecular basis for this transformation and its distribution among gut microorganisms are poorly understood. Here, we characterize a molybdenum-dependent enzyme from the human gut bacterium Eggerthella lenta that dehydroxylates catecholamine neurotransmitters. Our findings suggest that this activity enables E. lenta to use dopamine as an electron acceptor. We also identify candidate dehydroxylases that metabolize additional host- and plant-derived catechols. These dehydroxylases belong to a distinct group of largely uncharacterized molybdenum-dependent enzymes that likely mediate primary and secondary metabolism in multiple environments. Finally, we observe catechol dehydroxylation in the gut microbiotas of diverse mammals, confirming the presence of this chemistry in habitats beyond the human gut. These results suggest that the chemical strategies that mediate metabolism and interactions in the human gut are relevant to a broad range of species and habitats.
