Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism.
Actinobacteria
/ drug effects
Animals
Antiparkinson Agents
/ administration & dosage
Bacterial Proteins
/ antagonists & inhibitors
Decarboxylation
/ drug effects
Dopamine
/ metabolism
Enterococcus faecalis
/ drug effects
Gastrointestinal Microbiome
/ genetics
Genome, Bacterial
HeLa Cells
Humans
Levodopa
/ administration & dosage
Male
Metabolic Networks and Pathways
/ drug effects
Mice, Inbred BALB C
Tyrosine
/ administration & dosage
Tyrosine Decarboxylase
/ antagonists & inhibitors
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
14 06 2019
14 06 2019
Historique:
received:
29
06
2018
revised:
18
04
2019
accepted:
02
05
2019
entrez:
15
6
2019
pubmed:
15
6
2019
medline:
20
11
2019
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 31196984
pii: 364/6445/eaau6323
doi: 10.1126/science.aau6323
pmc: PMC7745125
pii:
doi:
Substances chimiques
Antiparkinson Agents
0
Bacterial Proteins
0
3-fluoro-alpha-fluoromethyltyrosine
160766-13-2
Tyrosine
42HK56048U
Levodopa
46627O600J
Tyrosine Decarboxylase
EC 4.1.1.25
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL122593
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007598
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019, American Association for the Advancement of Science.
Références
J Parkinsons Dis. 2017;7(s1):S3-S10
pubmed: 28282813
Food Microbiol. 2012 May;30(1):132-8
pubmed: 22265293
Appl Environ Microbiol. 2002 Jul;68(7):3537-44
pubmed: 12089039
Drug Metab Dispos. 2010 Jul;38(7):1166-76
pubmed: 20371637
Science. 2010 Nov 5;330(6005):831-5
pubmed: 21051639
Elife. 2018 May 15;7:
pubmed: 29761785
Cell. 2016 Dec 1;167(6):1469-1480.e12
pubmed: 27912057
PLoS One. 2013 Dec 10;8(12):e82562
pubmed: 24340040
Biochem J. 1964 Aug;92(2):300-8
pubmed: 5838073
J Biol Inorg Chem. 2015 Mar;20(2):349-72
pubmed: 25267303
Mov Disord. 2018 Jan;33(1):88-98
pubmed: 28843021
Nature. 2018 Jan 18;553(7688):291-294
pubmed: 29310122
P T. 2008 Oct;33(10):590-606
pubmed: 19750042
Science. 2019 Feb 8;363(6427):
pubmed: 30733391
Am J Clin Nutr. 1974 Nov;27(11):1348-55
pubmed: 4155602
mBio. 2015 Apr 14;6(2):
pubmed: 25873372
Lancet. 1974 Feb 16;1(7851):238-40
pubmed: 4130247
Br J Clin Pharmacol. 1974 Oct;1(5):417-24
pubmed: 22454921
Parkinsonism Relat Disord. 2016 Nov;32:66-72
pubmed: 27591074
J Pharmacol Exp Ther. 1973 Jul;186(1):160-6
pubmed: 4723308
Nat Struct Biol. 2001 Nov;8(11):963-7
pubmed: 11685243
Dan Med Bull. 1999 Jun;46(3):183-96
pubmed: 10421978
Science. 2017 Jun 23;356(6344):
pubmed: 28642381
Cell. 2016 Nov 3;167(4):915-932
pubmed: 27814521
Bull Exp Biol Med. 2017 Apr;162(6):734-737
pubmed: 28429209
Nature. 1978 Aug 31;274(5674):906-8
pubmed: 683331
J Biol Chem. 1957 Apr;225(2):615-21
pubmed: 13416264
Genome Med. 2017 Apr 28;9(1):39
pubmed: 28449715
J Clin Invest. 1973 Jul;52(7):1586-94
pubmed: 4718954
J Chromatogr. 1978 Jun 1;153(1):238-45
pubmed: 96122
Mov Disord. 2017 May;32(5):739-749
pubmed: 28195358
Xenobiotica. 1978 Oct;8(10):629-51
pubmed: 716472
Nat Commun. 2019 Jan 18;10(1):310
pubmed: 30659181
PLoS One. 2017 Nov 1;12(11):e0187307
pubmed: 29091972
Biochim Biophys Acta. 1989 Oct 13;993(1):108-15
pubmed: 2508758
J Clin Endocrinol Metab. 1997 Nov;82(11):3864-71
pubmed: 9360553
J Food Prot. 2008 Jan;71(1):93-101
pubmed: 18236668
mBio. 2019 Feb 5;10(1):
pubmed: 30723125
Proteomics. 2009 May;9(10):2695-710
pubmed: 19405032
J Neurosci. 2006 Mar 8;26(10):2798-807
pubmed: 16525059
Science. 2013 Jul 19;341(6143):295-8
pubmed: 23869020
Biol Chem. 2005 Oct;386(10):999-1006
pubmed: 16218872
Nat Rev Microbiol. 2016 Apr;14(5):273-87
pubmed: 26972811
Nature. 2018 Jan 11;553(7687):208-211
pubmed: 29323293
Annu Rev Biochem. 2004;73:383-415
pubmed: 15189147
Appl Microbiol Biotechnol. 2015 Apr;99(8):3547-58
pubmed: 25529314
Mov Disord. 2013 Aug;28(9):1241-9
pubmed: 23712625
ACS Chem Neurosci. 2014 Dec 17;5(12):1192-7
pubmed: 25270271
Lancet. 2014 Sep 27;384(9949):1196-205
pubmed: 24928805
Nature. 1971 Feb 5;229(5284):414-5
pubmed: 4926994
Nature. 1974 Feb 8;247(5440):364-6
pubmed: 4817854
Cell. 2017 May 18;169(5):849-861.e13
pubmed: 28502769
PLoS One. 2014 Nov 20;9(11):e112330
pubmed: 25411976
Mov Disord. 2015 Mar;30(3):350-8
pubmed: 25476529
N Engl J Med. 1972 Jan 6;286(1):8-14
pubmed: 4550085
Biochim Biophys Acta. 1950 Jan;4(1-3):130-7
pubmed: 15403918
JAMA. 1971 Dec 27;218(13):1912-4
pubmed: 5171067
Nature. 1960 Dec 3;188:849-50
pubmed: 13747445
J Food Prot. 2014 Apr;77(4):592-8
pubmed: 24680070
Sci Rep. 2016 Jun 13;6:27779
pubmed: 27292129