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

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.

Source: ScienceNOW - June 12, 2019 Category: Science Authors: Maini Rekdal, V., Bess, E. N., Bisanz, J. E., Turnbaugh, P. J., Balskus, E. P. Tags: Chemistry, Microbiology, Online Only r-articles Source Type: news