Gut microbes use diverse chemical reactions to metabolize many of the molecules we ingest, influencing their overall bioavailability and bioactivity. Our microbial co-inhabitants transform at least 50 different clinically used drugs including Levodopa (L-dopa), a dopamine precursor and the main treatment for Parkinson’s disease. Since the 1960s, it has been known that L-dopa is degraded by the gut microbiota. However, the specific microbe(s) and the enzyme(s) involved in L-dopa metabolism have remained elusive. Herein, we combine enrichment culturing, transcriptomics, and enzymology to identify and characterize the human-associated bacterial strains and enzymes degrading L-dopa. This work provides molecular insight into a widespread gut microbial metabolic pathway while also uncovering novel disease-relevant enzymes from the human gut. More broadly, our work may enable strategies for predicting and manipulating microbial chemistry in the human body and beyond.

Human gut microbes metabolize the Parkinson’s disease drug Levodopa

256th National Meeting (2018)

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