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

Vayu Maini Rekdal, Elizabeth N. Bess, Jordan E. Bisanz, Peter J. Turnbaugh, Emily P. Balskus

    Research output: Contribution to journalArticlepeer-review

    161 Scopus citations

    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.

    Original languageEnglish (US)
    Article numbereaau6323
    JournalScience
    Volume364
    Issue number6445
    DOIs
    StatePublished - Jun 14 2019

    All Science Journal Classification (ASJC) codes

    • General

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