General Information of Metabolite (ID: MT023)
  Meta Name
Riboflavin (B2)
  Unify Name
Riboflavin
  Synonym    Click to Show/Hide the Detailed Synonyms of This Metabolite
1-Deoxy-1-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)pentitol;6,7-Dimethyl-9-D-ribitylisoalloxazine;7,8-Dimethyl-10-(D-ribo-2,3,4,5-tetrahydroxypentyl)benzo[g]pteridine-2,4(3H,10H)-dione;7,8-Dimethyl-10-(D-ribo-2,3,4,5-tetrahydroxypentyl)isoalloxazine;7,8-Dimethyl-10-ribitylisoalloxazine;e101;Lactoflavin;Riboflavina;RIBOFLAVINE;Riboflavinum;Vitamin b2;Vitamin g;Bisulase;(-)-Riboflavin;1-Deoxy-1-(3,4-dihydro-7,8-dimethyl-2,4-dioxobenzo[g]pteridin-10(2H)-yl)-D-ribitol;6,7-Dimethyl-9-ribitylisoalloxazine;7,8-Dimethyl-10-(D-ribo-2,3,4,5-tetrahydroxypentyl)-benzo[g]pteridine-2,4(3H,10H)-dione;Beflavin;Beflavine;Benzo[g]pteridine riboflavin deriv.;e 101;Flavaxin;Flavin BB;Flaxain;FOOD Yellow 15;Hyre;Lactobene;Lactoflavine;Ribipca;Ribocrisina;Riboderm;Ribosyn;Ribotone;Ribovel;Russupteridine yellow III;San yellow b;Vitaflavine;Vitasan b2;Vitamin b 2
  Molecule Type
Vitamins
  Formula
C17H20N4O6
  Inchi Key
AUNGANRZJHBGPY-SCRDCRAPSA-N
  Description    Click to Show/Hide the Detailed Description of This Metabolite
Human Metabolome Database (HMDB): Riboflavin or vitamin B2 is an easily absorbed, water-soluble micronutrient with a key role in maintaining human health. Like the other B vitamins, it supports energy production by aiding in the metabolizing of fats, carbohydrates, and proteins. Vitamin B2 is also required for red blood cell formation and respiration, antibody production, and for regulating human growth and reproduction. It is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin is found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. Riboflavin is yellow or orange-yellow in color and in addition to being used as a food coloring it is also used to fortify some foods. It can be found in baby foods, breakfast cereals, sauces, processed cheese, fruit drinks and vitamin-enriched milk products. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as flavin mononucleotide and flavin adenine dinucleotide.
  External Links   HMDB ID   HMDB0000244
  VMH ID   ribflv
  KEGG ID   C00255
  Metlin ID   5249

The epigenetic modification information of this metabolite
Modification Type Molecule EM Info Cell/Tissue Type Modified sites Condition REF
DNA Methylation AGTR1 EM Info Peripheral blood leukocyte Promoter MTHFR C677T polymorphism [1], [2]
DNA Methylation GNA12 EM Info Peripheral blood leukocyte Promoter MTHFR C677T polymorphism [1], [3]
DNA Methylation IGF2 EM Info Peripheral blood leukocyte DMR2 MTHFR C677T polymorphism [1], [4]
DNA Methylation LINE-1 EM Info Peripheral blood leukocyte CpG sites MTHFR 677TT genotype [1], [5]
DNA Methylation MTHFR EM Info Peripheral blood leukocyte north shore MTHFR 677TT genotype [1], [4]
DNA Methylation Zac1 EM Info . . . [6], [7]
Histone Methylation H3K4 EM Info MGC-803 cells LSD1 Gastric cancer [1], [5]

The microbes that produce this metabolite
      Lactobacillus plantarum
         Detailed Information MIC Info click to show the detail information of this Microbiota [8], [9]
         Description
Lactiplantibacillus plantarum is a species of facultative anaerobic, gram-positive, saccharolytic; fermentative metabolism bacteria.
      Escherichia coli
         Detailed Information MIC Info click to show the detail information of this Microbiota [10]
         Description
Escherichia coli, also known as E. coli, is a gram-negative, facultative anaerobic, rod-shaped, coliform bacteria of the genus Escherichia.
      Bacteroidetes
         Detailed Information MIC Info click to show the detail information of this Microbiota [11], [12]
         Description
The phylum "Bacteroidetes" is composed of three large classes of gram-negative, nonsporeforming, anaerobic or aerobic, and rod-shaped bacteria that are widely distributed in the environment, including in soil, sediments, and sea water, as well as in the guts and on the skin of animals.
      Bifidobacterium
         Detailed Information MIC Info click to show the detail information of this Microbiota [1], [5]
         Description
Bifidobacteria is a genus of gram-positive, nonmotile, often branched anaerobic bacteria. They are ubiquitous inhabitants of the gastrointestinal tract, vagina and mouth of mammals, including humans.
      Bacillus subtilis
         Detailed Information MIC Info click to show the detail information of this Microbiota [1], [13]
         Description
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a gram-positive, catalase-positive bacteria, found in soil and the gastrointestinal tract of ruminants and humans.
      Fusobacteria
         Detailed Information MIC Info click to show the detail information of this Microbiota [1], [14]
         Description
Fusobacteria are obligately anaerobic non-sporeforming gram-negative bacilli.
      Proteobacteria
         Detailed Information MIC Info click to show the detail information of this Microbiota [1], [14]
         Description
Proteobacteria is a major phylum of gram-negative bacteria. It includes a wide variety of pathogenic genera, such as Escherichia, Salmonella, Vibrio, Helicobacter, Yersinia, Legionellales, and many others.
      Actinobacteria
         Detailed Information MIC Info click to show the detail information of this Microbiota [1], [14]
         Description
Actinobacteria are ubiquitous gram-positive bacteria with high guanine and cytosine contents in DNA, having a characteristic filamentous morphology.
      Bifidobacterium adolescentis
         Detailed Information MIC Info click to show the detail information of this Microbiota [15], [16]
         Description
Bifidobacteria adolescentis is a gram-positive bacteria that has no spores, no flagella, and does not move.
      Lactococcus lactis
         Detailed Information MIC Info click to show the detail information of this Microbiota [17], [18]
         Description
Lactococcus lactis is a facultative anaerobic, gram-positive non-sporulating and non-motile bacteria.
      Lactobacillus gasseri
         Detailed Information MIC Info click to show the detail information of this Microbiota [6], [7]
         Description
Lactobacillus gasseriis an anaerobic, gram-positive bacteria that falls into the category of lactic acid bacteria.
      Lactobacillus reuteri
         Detailed Information MIC Info click to show the detail information of this Microbiota [19], [20]
         Description
Lactobacillus reuteri is a facultative anaerobic, gram-positive bacteria that naturally inhabits the gut of mammals and birds.
      Lactobacillus plantarum M5MA1-B2
         Detailed Information MIC Info click to show the detail information of this Microbiota [21], [22]
         Description
Lactobacillus plantarum M5MA1 is a rod-shaped, gram-positive lactic acid bacteria. It is commonly found in the human and other mammalian gastrointestinal tracts, saliva, and various food products.
      Lactobacillus plantarum M5MA1
         Detailed Information MIC Info click to show the detail information of this Microbiota [21], [22]
         Description
Lactobacillus plantarum M5MA1 is a rod-shaped, gram-positive lactic acid bacteria. It is commonly found in the human and other mammalian gastrointestinal tracts, saliva, and various food products.
      Eremothecium ashbyii
         Detailed Information MIC Info click to show the detail information of this Microbiota [21], [7]
         Description
Eremothecium ashbyi is a riboflavin overproducing filamentous fungus in which the metabolic pathways have not been genetically characterized.
      Ashbya gossypii
         Detailed Information MIC Info click to show the detail information of this Microbiota [21], [7]
         Description
Eremothecium gossypii is a filamentous fungus or mold closely related to yeast, but growing exclusively in a filamentous way.
      Candida famata
         Detailed Information MIC Info click to show the detail information of this Microbiota [21], [7]
         Description
Debaryomyces hansenii is a species of yeast in the family Saccharomycetaceae. Also known as Candida famata, it accounts for up to 2% of invasive candidiasis cases.
      Lactobacillus
         Detailed Information MIC Info click to show the detail information of this Microbiota [11], [1]
         Description
Lactobacillus is a genus of gram-positive, facultative anaerobic or microaerophilic, rod-shaped, non-spore-forming bacteria. They are a major part of the lactic acid bacteria group. In humans, they constitute a significant component of the microbiota at a number of body sites, such as the digestive system, urinary system, and genital system.

References
1 Gut Microbiota as Important Mediator Between Diet and DNA Methylation and Histone Modifications in the Host. Nutrients. 2020 Feb 25;12(3):597. doi: 10.3390/nu12030597.
2 Biotinylation of histones represses transposable elements in human and mouse cells and cell lines and in Drosophila melanogaster. J Nutr. 2008 Dec;138(12):2316-22. doi: 10.3945/jn.108.098673.
3 Holocarboxylase synthetase regulates expression of biotin transporters by chromatin remodeling events at the SMVT locus. J Nutr Biochem. 2008 Jun;19(6):400-8. doi: 10.1016/j.jnutbio.2007.06.002. Epub 2007 Sep 27.
4 Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich's ataxia can be reduced upon HDAC inhibition by vitamin B3. Hum Mol Genet. 2013 Jul 1;22(13):2662-75. doi: 10.1093/hmg/ddt115. Epub 2013 Mar 7.
5 Arachidonic and oleic acid exert distinct effects on the DNA methylome. Epigenetics. 2016 May 3;11(5):321-34. doi: 10.1080/15592294.2016.1161873. Epub 2016 Apr 18.
6 Associations of dietary methyl donor intake with MLH1 promoter hypermethylation and related molecular phenotypes in sporadic colorectal cancer. Carcinogenesis. 2008 Sep;29(9):1765-73. doi: 10.1093/carcin/bgn074. Epub 2008 Mar 13.
7 Biosynthesis of Vitamins by Probiotic Bacteria.
8 Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia. Nat Commun. 2016 Jun 30;7:11960. doi: 10.1038/ncomms11960.
9 Dynamics and biodiversity of populations of lactic acid bacteria and acetic acid bacteria involved in spontaneous heap fermentation of cocoa beans in Ghana Appl Environ Microbiol. 2007 Mar;73(6):1809-24. doi: 10.1128/AEM.02189-06. Epub 2007 Feb 2.
10 Microbiota-derived metabolite promotes HDAC3 activity in the gut. Nature. 2020 Oct;586(7827):108-112. doi: 10.1038/s41586-020-2604-2. Epub 2020 Jul 30.
11 Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications. Sci Rep. 2021 Jan 28;11(1):2519. doi: 10.1038/s41598-021-81620-x.
12 Dietary proline supplementation alters colonic luminal microbiota and bacterial metabolite composition between days 45 and 70 of pregnancy in Huanjiang mini-pigs J Anim Sci Biotechnol. 2018 Jan 30;9:18. doi: 10.1186/s40104-018-0233-5. eCollection 2018.
13 Riboflavin supplementation alters global and gene-specific DNA methylation in adults with the MTHFR 677 TT genotype. Biochimie. 2020 Jun;173:17-26. doi: 10.1016/j.biochi.2020.04.007. Epub 2020 Apr 22.
14 DNA methylation of hypertension-related genes and effect of riboflavin supplementation in adults stratified by genotype for the MTHFR C677T polymorphism. Int J Cardiol. 2021 Jan 1;322:233-239. doi: 10.1016/j.ijcard.2020.09.011. Epub 2020 Sep 10.
15 Butyrate drives the acetylation of histone H3K9 to activate steroidogenesis through PPAR-gamma and PGC1-alpha pathways in ovarian granulosa cells. FASEB J. 2021 Feb;35(2):e21316. doi: 10.1096/fj.202000444R.
16 The Gut Microbiota from Lean and Obese Subjects Contribute Differently to the Fermentation of Arabinogalactan and Inulin PLoS One. 2016 Jul 13;11(7):e0159236. doi: 10.1371/journal.pone.0159236. eCollection 2016.
17 Response of MiRNA-22-3p and MiRNA-149-5p to Folate Deficiency and the Differential Regulation of MTHFR Expression in Normal and Cancerous Human Hepatocytes. PLoS One. 2017 Jan 3;12(1):e0168049. doi: 10.1371/journal.pone.0168049. eCollection 2017.
18 Riboflavin production in Lactococcus lactis: potential for in situ production of vitamin-enriched foods Appl Environ Microbiol. 2004 Oct;70(10):5769-77. doi: 10.1128/AEM.70.10.5769-5777.2004.
19 Spermidine inhibits MMP-2 via modulation of histone acetyltransferase and histone deacetylase in HDFs. Int J Biol Macromol. 2012 Dec;51(5):1003-7. doi: 10.1016/j.ijbiomac.2012.08.013. Epub 2012 Aug 25.
20 Human Breast Milk Promotes the Secretion of Potentially Beneficial Metabolites by Probiotic Lactobacillus reuteri DSM 17938 Nutrients. 2019 Jul 9;11(7):1548. doi: 10.3390/nu11071548.
21 Dietary metabolites derived from gut microbiota: critical modulators of epigenetic changes in mammals. Nutr Rev. 2017 May 1;75(5):374-389. doi: 10.1093/nutrit/nux001.
22 Real-Time Detection of Riboflavin Production by Lactobacillus plantarum Strains and Tracking of Their Gastrointestinal Survival and Functionality in vitro and in vivo Using mCherry Labeling Front Microbiol. 2019 Jul 31;10:1748. doi: 10.3389/fmicb.2019.01748. eCollection 2019.

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