A widely distributed metalloenzyme class enables gut microbial metabolism of host- and diet-derived catechols

Abstract

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.

The microbiota–gut–brain axis: pathways to better brain health. Perspectives on what we know, what we need to investigate and how to put knowledge into practice

“…Disorders associated with dopamine deficiency include addiction, schizophrenia, and Parkinson’s disease. Research suggests that certain bacteria produce [ 13 ] or metabolise [ 50 ] dopamine.…”

Mammalian gut metabolomes mirror microbiome composition and host phylogeny

“…This degradation process has been demonstrated in vitro by the incubation of the parent compounds with fecal slurries [ 84 ], and a handful of rumen and fecal isolate strains have been shown to degrade quercetin into 3, 4-dihydroxyphenylacetate, which can then be dehydroxylated to form 3-hydroxyphenylacetate [ 85 , 86 ]. Recently, a gut dopamine dehydroxylase has been reported in Eggerthella lenta [ 87 ], and a follow-up study characterizing related catechol dehydroxylases showed that the conversion to 3-hydroxyphenylacetate is performed by a number of strains, including E. lenta and two Gordonibacter strains [ 88 ]. As shown above, in the LC–MS/MS metabolomics analysis, two classes of plant-derived compounds, triterpenoids and flavonoids, were enriched in the Perissodactyla and Artiodactyla (Fig.…”

Conceptual Exchanges for Understanding Free-Living and Host-Associated Microbiomes

“…Despite the centrality of fermentative processes within the mammalian gut, evidence that unconventional respiratory electron mechanisms may have important roles has begun to mount. Recent demonstration that flavins can facilitate electron acceptor usage ( 33 ) and that dopamine can be a respiratory electron acceptor ( 39 ) and past suggestions that cholesterol can also function in this capacity ( 40 ) indicate that we have much to learn about microbial adaptation to host environments. The human gut is not unique in its surplus of carbon and deficit of inorganic electron acceptors; environments such as salt marshes, peat bogs, and soils also have these characteristics ( Fig.…”