Two‐carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation. Issue 3 (19th November 2018)
- Record Type:
- Journal Article
- Title:
- Two‐carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation. Issue 3 (19th November 2018)
- Main Title:
- Two‐carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation
- Authors:
- Röth, Daniel
Chiang, Abby J.
Hu, Weidong
Gugiu, Gabriel B.
Morra, Christina N.
Versalovic, James
Kalkum, Markus - Abstract:
- ABSTRACT: Colonization of the gut by certain probiotic Lactobacillus reuteri strains has been associated with reduced risk of inflammatory diseases and colorectal cancer. Previous studies pointed to a functional link between immunomodulation, histamine production, and folate metabolism, the central 1‐carbon pathway for the transfer of methyl groups. Using mass spectrometry and NMR spectroscopy, we analyzed folate metabolites of L. reuteri strain 6475 and discovered that the bacterium produces a 2‐carbon‐transporting folate in the form of 5, 10‐ethenyl‐tetrahydrofolyl polyglutamate. Isotopic labeling permitted us to trace the source of the 2‐carbon unit back to acetate of the culture medium. We show that the 2C folate cycle of L. reuteri is capable of transferring 2 carbon atoms to homocysteine to generate the unconventional amino acid ethionine, a known immunomodulator. When we treated monocytic THP‐1 cells with ethionine, their transcription of TNF‐α was inhibited and cell proliferation reduced. Mass spectrometry of THP‐1 histones revealed incorporation of ethionine instead of methionine into proteins, a reduction of histone‐methylation, and ethylation of histone lysine residues. Our findings suggest that the microbiome can expose the host to ethionine through a novel 2‐carbon transporting variant of the folate cycle and modify human chromatin via ethylation.—Roth, D., Chiang, A. J., Hu, W., Gugiu, G. B., Morra, C. N., Versalovic, J., Kalkum, M. The two‐carbon folate cycleABSTRACT: Colonization of the gut by certain probiotic Lactobacillus reuteri strains has been associated with reduced risk of inflammatory diseases and colorectal cancer. Previous studies pointed to a functional link between immunomodulation, histamine production, and folate metabolism, the central 1‐carbon pathway for the transfer of methyl groups. Using mass spectrometry and NMR spectroscopy, we analyzed folate metabolites of L. reuteri strain 6475 and discovered that the bacterium produces a 2‐carbon‐transporting folate in the form of 5, 10‐ethenyl‐tetrahydrofolyl polyglutamate. Isotopic labeling permitted us to trace the source of the 2‐carbon unit back to acetate of the culture medium. We show that the 2C folate cycle of L. reuteri is capable of transferring 2 carbon atoms to homocysteine to generate the unconventional amino acid ethionine, a known immunomodulator. When we treated monocytic THP‐1 cells with ethionine, their transcription of TNF‐α was inhibited and cell proliferation reduced. Mass spectrometry of THP‐1 histones revealed incorporation of ethionine instead of methionine into proteins, a reduction of histone‐methylation, and ethylation of histone lysine residues. Our findings suggest that the microbiome can expose the host to ethionine through a novel 2‐carbon transporting variant of the folate cycle and modify human chromatin via ethylation.—Roth, D., Chiang, A. J., Hu, W., Gugiu, G. B., Morra, C. N., Versalovic, J., Kalkum, M. The two‐carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation. FASEB J. 33, 3536‐3548 (2019). www.fasebj.org … (more)
- Is Part Of:
- FASEB journal. Volume 33:Issue 3(2019)
- Journal:
- FASEB journal
- Issue:
- Volume 33:Issue 3(2019)
- Issue Display:
- Volume 33, Issue 3 (2019)
- Year:
- 2019
- Volume:
- 33
- Issue:
- 3
- Issue Sort Value:
- 2019-0033-0003-0000
- Page Start:
- 3536
- Page End:
- 3548
- Publication Date:
- 2018-11-19
- Subjects:
- ethenyltetrahydrofolate -- probiotic bacteria -- microbiome -- posttranslational modification -- lysine ethylation
Biology -- Periodicals
Biology, Experimental -- Periodicals
570 - Journal URLs:
- http://onlinelibrary.wiley.com/ ↗
- DOI:
- 10.1096/fj.201801848R ↗
- Languages:
- English
- ISSNs:
- 0892-6638
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - BLDSS-3PM
British Library HMNTS - ELD Digital store - Ingest File:
- 13226.xml