دورية أكاديمية
أعرض في EDS

A widely distributed metalloenzyme class enables gut microbial metabolism of host- and diet-derived catechols.

التفاصيل البيبلوغرافية
العنوان: A widely distributed metalloenzyme class enables gut microbial metabolism of host- and diet-derived catechols.
المؤلفون: Maini Rekdal V; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States., Nol Bernadino P; Department of Chemistry and Molecular Biology, University of California, Irvine, Irvine, United States.; Department of Chemistry and Molecular Biochemistry, University of California, Irvine, Irvine, United States., Luescher MU; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States., Kiamehr S; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States., Le C; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States., Bisanz JE; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States., Turnbaugh PJ; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States.; Chan Zuckerberg Biohub, San Francisco, United States., Bess EN; Department of Chemistry and Molecular Biology, University of California, Irvine, Irvine, United States.; Department of Chemistry and Molecular Biochemistry, University of California, Irvine, Irvine, United States., Balskus EP; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States.
المصدر: ELife [Elife] 2020 Feb 18; Vol. 9. Date of Electronic Publication: 2020 Feb 18.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Diet* , Gastrointestinal Microbiome*, Catechols/*metabolism , Enzymes/*metabolism , Metalloproteins/*metabolism, Humans
مستخلص: Catechol dehydroxylation is a central chemical transformation in the gut microbial metabolism of plant- and host-derived small molecules. However, the molecular basis for this transformation and its distribution among gut microorganisms are poorly understood. Here, we characterize a molybdenum-dependent enzyme from the human gut bacterium Eggerthella lenta that dehydroxylates catecholamine neurotransmitters. Our findings suggest that this activity enables E. lenta to use dopamine as an electron acceptor. We also identify candidate dehydroxylases that metabolize additional host- and plant-derived catechols. These dehydroxylases belong to a distinct group of largely uncharacterized molybdenum-dependent enzymes that likely mediate primary and secondary metabolism in multiple environments. Finally, we observe catechol dehydroxylation in the gut microbiotas of diverse mammals, confirming the presence of this chemistry in habitats beyond the human gut. These results suggest that the chemical strategies that mediate metabolism and interactions in the human gut are relevant to a broad range of species and habitats.
Competing Interests: VM, PN, ML, SK, CL, JB, EB No competing interests declared, PT Reviewing editor, eLife, EB has consulted for Merck, Novartis, and Kintai Therapeutics; is on the Scientific Advisory Boards of Kintai Therapeutics and Caribou Biosciences.
(© 2020, Maini Rekdal et al.)
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معلومات مُعتمدة: T32 GM007598 United States GM NIGMS NIH HHS; P30 DK098722 United States DK NIDDK NIH HHS; 5T32GM007598-38 United States NH NIH HHS; M01 RR001271 United States RR NCRR NIH HHS
فهرسة مساهمة: Keywords: Eggerthella lenta; Gordonibacter sp.; biochemistry; catechol dehydroxylase; chemical biology; infectious disease; microbiology; molybdenum enzyme
Local Abstract: [plain-language-summary] Inside the human gut there are trillions of bacteria. These microbes are critical for breaking down and modifying molecules that the body consumes (such as nutrients and drugs) and produces (such as hormones). Although metabolizing these molecules is known to impact health and disease, little is known about the specific components, such as the genes and enzymes, involved in these reactions. A prominent microbial reaction in the gut metabolizes molecules by removing a hydroxyl group from an aromatic ring and replacing it with a hydrogen atom. This chemical reaction influences the fate of dietary compounds, clinically used drugs and chemicals which transmit signals between nerves (neurotransmitters). But even though this reaction was discovered over 50 years ago, it remained unknown which microbial enzymes are directly responsible for this metabolism. In 2019, researchers discovered the human gut bacteria Eggerthella lenta produces an enzyme named Dadh that can remove a hydroxyl group from the neurotransmitter dopamine. Now, Maini Rekdal et al. – including many of the researchers involved in the 2019 study – have used a range of different experiments to further characterize this enzyme and see if it can break down molecules other than dopamine. This revealed that Dadh specifically degrades dopamine, and this process promotes E. lenta growth. Next, Maini Rekdal et al. uncovered a group of enzymes that had similar characteristics to Dadh and could metabolize molecules other than dopamine, including molecules derived from plants and nutrients in food. These Dadh-like enzymes were found not only in the guts of humans, but in other organisms and environments, including the soil, ocean and plants. Plant-derived molecules are associated with human health, and the discovery of the enzymes that break down these products could provide new insights into the health effects of plant-based foods. In addition, the finding that gut bacteria harbor a dopamine metabolizing enzyme has implications for the interaction between the gut microbiome and the nervous system, which has been linked to human health and disease. These newly discovered enzymes are also involved in metabolic reactions outside the human body. Future work investigating the mechanisms and outputs of these reactions could improve current strategies for degrading pollutants and producing medically useful molecules.
المشرفين على المادة: 0 (Catechols)
0 (Enzymes)
0 (Metalloproteins)
تواريخ الأحداث: Date Created: 20200219 Date Completed: 20210414 Latest Revision: 20240331
رمز التحديث: 20240331
مُعرف محوري في PubMed: PMC7028382
DOI: 10.7554/eLife.50845
PMID: 32067637
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.50845