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Cited by 753Parkinson's Disease Mechanisms and TreatmentsGut microbiota and healthPolyamine Metabolism and Applications

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

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Maini Rekdal, Vayu, Bess, Elizabeth N., Bisanz, Jordan E., Turnbaugh, Peter J., Balskus, Emily P.·2019·Science
DOI 10.1126/science.aau6323PMC PMC7745125
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Abstract

The dope on l -dopa metabolism: The efficacy of l -dopa treatment for Parkinson's disease is hugely variable between individuals, depending on the composition of their microbiota. l -Dopa is decarboxylated into active dopamine, but if the gut microbiota metabolize l -dopa before it crosses the blood-brain barrier, medication is ineffective. Maini Rekdal et al. found that different species of bacterium are involved in l -dopa metabolism (see the Perspective by O'Neill). Tyrosine decarboxylase (TDC) from Enterococcus faecalis and dopamine dehydroxylase (Dadh) from Eggerthella lenta A2 sequentially metabolized l -dopa into m -tyramine. The microbial l -dopa decarboxylase can be inactivated by ( S )-α-fluoromethyltyrosine (AFMT), which indicates possibilities for developing combinations of Parkinson's drugs to circumvent microbial inactivation. Science , this issue p. eaau6323 ; see also p. 1030

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Authors
Maini Rekdal, V., Bess, E. N., Bisanz, J. E., Turnbaugh, P. J., & Balskus, E. P.
Affiliations
  • Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
  • University of California, San Francisco (US)
  • Harvard University (US)
Corresponding author
  • Turnbaugh, Peter J.
  • Balskus, Emily P.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2019-06-14
Volume
364
Issue
6445
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aau6323
PMC
PMC7745125
OpenAlex
W2951517287
Cited by
753
References
11
Citations by year
2026: 101 · 2025: 109 · 2024: 117 · 2023: 109 · 2022: 109 · 2021: 100 · 2020: 85 · 2019: 20 · 2018: 2 · 2013: 1
FWCI
53.13
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Funders
  • National Science Foundation
  • National Institutes of Health (R01HL122593, 5T32GM007598-38)
  • David and Lucile Packard Foundation (2013-39267)
  • Howard Hughes Medical Institute
  • Bill and Melinda Gates Foundation (OPP1158186)
  • Life Sciences Research Foundation
  • Natural Sciences and Engineering Research Council of Canada
  • Chan Zuckerberg Biohub
  • Arthritis Foundation
  • Damon Runyon Cancer Research Foundation (DRR-42-16)
  • Kinship Foundation (SSP-2016-1352)
  • Rheumatology Research Foundation
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
Keywords
levodopa metabolism, gut microbiota, Parkinson's disease, tyrosine decarboxylase, Enterococcus faecalis, Eggerthella lenta, m-tyramine, drug resistance, blood-brain barrier
MeSH terms
Gastrointestinal Microbiome, Animals, Antiparkinson Agents, Bacterial Proteins, Decarboxylation, Dopamine, HeLa Cells, Humans, Levodopa, Male, Mice, Inbred BALB C, Enterococcus faecalis, Tyrosine, Tyrosine Decarboxylase, Genome, Bacterial, Actinobacteria, Metabolic Networks and Pathways

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