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

TitleDiscovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine.
Publication TypeJournal Article
Year of Publication2014
AuthorsWilliams, BB, Van Benschoten, AH, Cimermancic, P, Donia, MS, Zimmermann, M, Taketani, M, Ishihara, A, Kashyap, PC, Fraser, JS, Fischbach, MA
JournalCell Host Microbe
Volume16
Issue4
Pagination495-503
Date Published2014 Oct 8
ISSN1934-6069
KeywordsAmino Acid Sequence, Bacteria, Biotransformation, Carboxy-Lyases, Crystallography, X-Ray, Gastrointestinal Tract, Humans, Metagenome, Microbiota, Models, Molecular, Molecular Sequence Data, Neurotransmitter Agents, Phylogeny, Protein Conformation, Sequence Homology, Tryptamines, Tryptophan
Abstract

<p>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.</p>

DOI10.1016/j.chom.2014.09.001
Alternate JournalCell Host Microbe
PubMed ID25263219
PubMed Central IDPMC4260654
Grant ListDP2 OD007290 / OD / NIH HHS / United States
GM081879 / GM / NIGMS NIH HHS / United States
T32 GM008284 / GM / NIGMS NIH HHS / United States
T32 GM067547 / GM / NIGMS NIH HHS / United States
P50 GM081879 / GM / NIGMS NIH HHS / United States
OD007290 / OD / NIH HHS / United States
T32 EB009383 / EB / NIBIB NIH HHS / United States
K08 DK100638 / DK / NIDDK NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
OD009180 / OD / NIH HHS / United States
DP5 OD009180 / OD / NIH HHS / United States
K08DK100638 / DK / NIDDK NIH HHS / United States
T32 GM064337 / GM / NIGMS NIH HHS / United States
P30 DK084567 / DK / NIDDK NIH HHS / United States