title: 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 β-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.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Brianna B
authors.initials: BB
authors.lastname: Williams
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Van Benschoten
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Cimermancic
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Donia
authors.affiliation: ETH Zurich, Institute of Molecular Systems Biology, Zurich 8093, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Mao
authors.initials: M
authors.lastname: Taketani
authors.affiliation: Faculty of Agriculture, Tottori University, Koyama, Tottori 680-8550, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishihara
authors.affiliation: Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Purna C
authors.initials: PC
authors.lastname: Kashyap
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Fraser
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: fischbach@fischbachgroup.org.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fischbach
mesh_terms: D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D001711:Biotransformation; D002262:Carboxy-Lyases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018360:Crystallography, X-Ray; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D054892:Metagenome; D064307:Microbiota; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010802:Phylogeny; D011487:Protein Conformation; D017385:Sequence Homology; D014363:Tryptamines / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D014363:Tryptamines; C030820:tryptamine; D014364:Tryptophan; D002262:Carboxy-Lyases