Format

Send to

Choose Destination
Science. 2019 Jun 14;364(6445). pii: eaau6323. doi: 10.1126/science.aau6323.

Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism.

Author information

1
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
2
Department of Microbiology and Immunology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
3
Department of Chemistry, University of California, Irvine, 1102 Natural Sciences 2, Irvine, CA 92617, USA.
4
Department of Molecular Biology and Biochemistry, University of California, Irvine, 1102 Natural Sciences 2, Irvine, CA 92617, USA.
5
Department of Microbiology and Immunology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. balskus@chemistry.harvard.edu peter.turnbaugh@ucsf.edu.
6
Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
7
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA. balskus@chemistry.harvard.edu peter.turnbaugh@ucsf.edu.

Abstract

The human gut microbiota metabolizes the Parkinson's disease medication Levodopa (l-dopa), potentially reducing drug availability and causing side effects. However, the organisms, genes, and enzymes responsible for this activity in patients and their susceptibility to inhibition by host-targeted drugs are unknown. Here, we describe an interspecies pathway for gut bacterial l-dopa metabolism. Conversion of l-dopa to dopamine by a pyridoxal phosphate-dependent tyrosine decarboxylase from Enterococcus faecalis is followed by transformation of dopamine to m-tyramine by a molybdenum-dependent dehydroxylase from Eggerthella lenta These enzymes predict drug metabolism in complex human gut microbiotas. Although a drug that targets host aromatic amino acid decarboxylase does not prevent gut microbial l-dopa decarboxylation, we identified a compound that inhibits this activity in Parkinson's patient microbiotas and increases l-dopa bioavailability in mice.

PMID:
31196984
DOI:
10.1126/science.aau6323
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center