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Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine.


ABSTRACT: Several recent studies describe the influence of the gut microbiota on host brain and behavior. However, the mechanisms responsible for microbiota-nervous system interactions are largely unknown. Using a combination of genetics, biochemistry, and crystallography, we identify and characterize two phylogenetically distinct enzymes found in the human microbiome that decarboxylate tryptophan to form the ?-arylamine neurotransmitter tryptamine. Although this enzymatic activity is exceedingly rare among bacteria more broadly, analysis of the Human Microbiome Project data demonstrate that at least 10% of the human population harbors at least one bacterium encoding a tryptophan decarboxylase in their gut community. Our results uncover a previously unrecognized enzymatic activity that can give rise to host-modulatory compounds and suggests a potential direct mechanism by which gut microbiota can influence host physiology, including behavior.

SUBMITTER: Williams BB 

PROVIDER: S-EPMC4260654 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine.

Williams Brianna B BB   Van Benschoten Andrew H AH   Cimermancic Peter P   Donia Mohamed S MS   Zimmermann Michael M   Taketani Mao M   Ishihara Atsushi A   Kashyap Purna C PC   Fraser James S JS   Fischbach Michael A MA  

Cell host & microbe 20140925 4


Several recent studies describe the influence of the gut microbiota on host brain and behavior. However, the mechanisms responsible for microbiota-nervous system interactions are largely unknown. Using a combination of genetics, biochemistry, and crystallography, we identify and characterize two phylogenetically distinct enzymes found in the human microbiome that decarboxylate tryptophan to form the β-arylamine neurotransmitter tryptamine. Although this enzymatic activity is exceedingly rare amo  ...[more]

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