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

Title	Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism
Authors	Vayu Maini Rekdal, Elizabeth N. Bess, Jordan E. Bisanz, Peter J. Turnbaugh, Emily P. Balskus
Magazine	Science (New York, N.y.)
Date	06/14/2019
DOI	10.1126/science.aau6323
Introduction	The human gut microbiota processes the Parkinson's disease medication Levodopa (L-dopa), which can reduce drug availability and lead to side effects. However, the specific organisms, genes, and enzymes responsible for this activity in patients, and their susceptibility to inhibition by host-targeted drugs, remain uncharacterised. This study outlines an interspecies pathway for gut bacterial L-dopa metabolism. L-dopa is converted to dopamine by a pyridoxal phosphate-dependent tyrosine decarboxylase from Enterococcus faecalis, subsequently transformed to m-tyramine by a molybdenum-dependent dehydroxylase from Eggerthella lenta. These enzymes serve as predictors for drug metabolism in complex human gut microbiotas. While a drug targeting host aromatic amino acid decarboxylase does not prevent gut microbial L-dopa decarboxylation, a compound was identified that suppresses this activity in Parkinson's patient microbiotas and enhances L-dopa bioavailability in mice.
Quote	Vayu Maini Rekdal, Elizabeth N. Bess and Jordan E. Bisanz et al. Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science (New York, N.Y.). 2019. Vol. 364(6445). DOI: 10.1126/science.aau6323
Element	Molybdenum (Mo) , Fluorine (F)
Materials	Chemical Compounds
Topics	Biomedical Materials , Catalytic Materials
Industry	Chemical & Pharmacy , Pharmaceutical Industry , Research & Laboratory