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Title: A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase

Abstract

COG5598 comprises a large number of proteins related to MttB, the trimethylamine:corrinoid methyltransferase. MttB has a genetically encoded pyrrolysine residue proposed essential for catalysis. MttB is the only known trimethylamine methyltransferase, yet the great majority of members of COG5598 lack pyrrolysine, leaving the activity of these proteins an open question. Here, we describe the function of one of the nonpyrrolysine members of this large protein family. Three nonpyrrolysine MttB homologs are encoded in Desulfitobacterium hafniense, a Gram-positive strict anaerobe present in both the environment and human intestine. D. hafniense was found capable of growth on glycine betaine with electron acceptors such as nitrate or fumarate, producing dimethylglycine and CO2 as products. Examination of the genome revealed genes for tetrahydrofolate-linked oxidation of a methyl group originating from a methylated corrinoid protein, but no obvious means to carry out corrinoid methylation with glycine betaine. DSY3156, encoding one of the nonpyrrolysine MttB homologs, was up-regulated during growth on glycine betaine. The recombinant DSY3156 protein converts glycine betaine and cob(I)alamin to dimethylglycine and methylcobalamin. To our knowledge, DSY3156 is the first glycine betaine:corrinoid methyltransferase described, and a designation of MtgB is proposed. Additionally, DSY3157, an adjacently encoded protein, was shown to be a methylcobalamin:tetrahydrofolatemore » methyltransferase and is designated MtgA. Homologs of MtgB are widely distributed, especially in marine bacterioplankton and nitrogen-fixing plant symbionts. Lastly, they are also found in multiple members of the human microbiome, and may play a beneficial role in trimethylamine homeostasis, which in recent years has been directly tied to human cardiovascular health.« less

Authors:
 [1];  [2];  [2];  [3];  [4]
  1. Miami Univ., Oxford, OH (United States). Dept. of Microbiology
  2. The Ohio State Univ., Columbus, OH (United States). Dept. of Microbiology
  3. The Ohio State Univ., Columbus, OH (United States). Dept. of Microbiology and Biochemistry Program
  4. Miami Univ., Oxford, OH (United States). Dept. of Microbiology; Miami Univ., Hamilton, OH (United States)
Publication Date:
Research Org.:
The Ohio State Univ., Columbus, OH (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1348916
Grant/Contract Number:  
FG02-91ER20042
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 111; Journal Issue: 43; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; glycine betaine; trimethylamine methyltransferase; COG5598; L-pyrrolysine; Desulfitobacterium hafniense

Citation Formats

Ticak, Tomislav, Kountz, D. J., Girosky, K. E., Krzycki, J. A., and Ferguson, D. J. A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase. United States: N. p., 2014. Web. doi:10.1073/pnas.1409642111.
Ticak, Tomislav, Kountz, D. J., Girosky, K. E., Krzycki, J. A., & Ferguson, D. J. A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase. United States. https://doi.org/10.1073/pnas.1409642111
Ticak, Tomislav, Kountz, D. J., Girosky, K. E., Krzycki, J. A., and Ferguson, D. J. Mon . "A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase". United States. https://doi.org/10.1073/pnas.1409642111. https://www.osti.gov/servlets/purl/1348916.
@article{osti_1348916,
title = {A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase},
author = {Ticak, Tomislav and Kountz, D. J. and Girosky, K. E. and Krzycki, J. A. and Ferguson, D. J.},
abstractNote = {COG5598 comprises a large number of proteins related to MttB, the trimethylamine:corrinoid methyltransferase. MttB has a genetically encoded pyrrolysine residue proposed essential for catalysis. MttB is the only known trimethylamine methyltransferase, yet the great majority of members of COG5598 lack pyrrolysine, leaving the activity of these proteins an open question. Here, we describe the function of one of the nonpyrrolysine members of this large protein family. Three nonpyrrolysine MttB homologs are encoded in Desulfitobacterium hafniense, a Gram-positive strict anaerobe present in both the environment and human intestine. D. hafniense was found capable of growth on glycine betaine with electron acceptors such as nitrate or fumarate, producing dimethylglycine and CO2 as products. Examination of the genome revealed genes for tetrahydrofolate-linked oxidation of a methyl group originating from a methylated corrinoid protein, but no obvious means to carry out corrinoid methylation with glycine betaine. DSY3156, encoding one of the nonpyrrolysine MttB homologs, was up-regulated during growth on glycine betaine. The recombinant DSY3156 protein converts glycine betaine and cob(I)alamin to dimethylglycine and methylcobalamin. To our knowledge, DSY3156 is the first glycine betaine:corrinoid methyltransferase described, and a designation of MtgB is proposed. Additionally, DSY3157, an adjacently encoded protein, was shown to be a methylcobalamin:tetrahydrofolate methyltransferase and is designated MtgA. Homologs of MtgB are widely distributed, especially in marine bacterioplankton and nitrogen-fixing plant symbionts. Lastly, they are also found in multiple members of the human microbiome, and may play a beneficial role in trimethylamine homeostasis, which in recent years has been directly tied to human cardiovascular health.},
doi = {10.1073/pnas.1409642111},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 43,
volume = 111,
place = {United States},
year = {Mon Oct 13 00:00:00 EDT 2014},
month = {Mon Oct 13 00:00:00 EDT 2014}
}

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Works referenced in this record:

A Desulfitobacterium strain isolated from human feces that does not dechlorinate chloroethenes or chlorophenols
journal, November 2001

  • Pas, Bram; Harmsen, Hermie; Raangs, Gerwin
  • Archives of Microbiology, Vol. 176, Issue 5
  • DOI: 10.1007/s002030100334

Studies of Dimethylglycine Oxidase Isoenzymes in Arthrobacter globiformis Cells
journal, December 2010

  • Časaitė, Vida; Povilonienė, Simona; Meškienė, Rita
  • Current Microbiology, Vol. 62, Issue 4
  • DOI: 10.1007/s00284-010-9852-6

Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
journal, August 1970


Homeostasis and Catabolism of Choline and Glycine Betaine: Lessons from Pseudomonas aeruginosa
journal, January 2013

  • Wargo, Matthew J.
  • Applied and Environmental Microbiology, Vol. 79, Issue 7
  • DOI: 10.1128/AEM.03565-12

Dissimilatory reduction of nitrate in seawater by a Methylophaga strain containing two highly divergent narG sequences
journal, April 2010

  • Auclair, Julie; Lépine, François; Parent, Serge
  • The ISME Journal, Vol. 4, Issue 10
  • DOI: 10.1038/ismej.2010.47

Metaproteomic Survey of Six Aquatic Habitats: Discovering the Identities of Microbial Populations Active in Biogeochemical Cycling
journal, January 2014


Glycine metabolism in anaerobes
journal, January 1994


Regulatory Factors Associated with Synthesis of the Osmolyte Glycine Betaine in the Halophilic MethanoarchaeonMethanohalophilus portucalensis
journal, February 1999


Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
journal, December 2001


The Expanding World of Methylotrophic Metabolism
journal, October 2009


Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide
journal, February 2014


Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme
journal, November 2012

  • Craciun, S.; Balskus, E. P.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 52
  • DOI: 10.1073/pnas.1215689109

Metabolic changes of rhizobia in legume nodules
journal, April 2006


Reconstitution of Dimethylamine:Coenzyme M Methyl Transfer with a Discrete Corrinoid Protein and Two Methyltransferases Purified from Methanosarcina barkeri
journal, June 2000

  • Ferguson, Donald J.; Gorlatova, Natalia; Grahame, David A.
  • Journal of Biological Chemistry, Vol. 275, Issue 37
  • DOI: 10.1074/jbc.M910218199

Occurrence of Choline and Glycine Betaine Uptake and Metabolism in the Family Rhizobiaceae and Their Roles in Osmoprotection
journal, May 1999

  • Boncompagni, Eric; Østerås, Magne; Poggi, Marie-Christine
  • Applied and Environmental Microbiology, Vol. 65, Issue 5
  • DOI: 10.1128/AEM.65.5.2072-2077.1999

A Desulfitobacterium strain isolated from human feces that does not dechlorinate chloroethenes or chlorophenols
journal, June 2001

  • van de Pas, Bram; Harmsen, Hermie; Raangs, Gerwin
  • Archives of Microbiology, Vol. 175, Issue 6
  • DOI: 10.1007/s002030100276

Betaine Fermentation and Oxidation by Marine Desulfuromonas Strains
journal, January 1989


The rapid generation of mutation data matrices from protein sequences
journal, January 1992


Betaine: New Oxidant in the Stickland Reaction and Methanogenesis from Betaine and l-Alanine by a Clostridium sporogenes-Methanosarcina barkeri Coculture
journal, January 1983


Stability and Robustness of Human Metabolic Phenotypes in Response to Sequential Food Challenges
journal, December 2011

  • Heinzmann, Silke S.; Merrifield, Claire A.; Rezzi, Serge
  • Journal of Proteome Research, Vol. 11, Issue 2
  • DOI: 10.1021/pr2005764

Pyrrolysine Encoded by UAG in Archaea: Charging of a UAG-Decoding Specialized tRNA
journal, May 2002


Trimethylamine N-oxide metabolism by abundant marine heterotrophic bacteria
journal, February 2014

  • Lidbury, I.; Murrell, J. C.; Chen, Y.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 7
  • DOI: 10.1073/pnas.1317834111

Function of genetically encoded pyrrolysine in corrinoid-dependent methylamine methyltransferases
journal, October 2004


Characterization of an O-Demethylase of Desulfitobacterium hafniense DCB-2
journal, April 2012

  • Studenik, S.; Vogel, M.; Diekert, G.
  • Journal of Bacteriology, Vol. 194, Issue 13, p. 3317-3326
  • DOI: 10.1128/JB.00146-12

Carnitine: An osmolyte that plays a metabolic role
journal, January 2000


MUSCLE: multiple sequence alignment with high accuracy and high throughput
journal, March 2004

  • Edgar, R. C.
  • Nucleic Acids Research, Vol. 32, Issue 5, p. 1792-1797
  • DOI: 10.1093/nar/gkh340

Potential for Chemolithoautotrophy Among Ubiquitous Bacteria Lineages in the Dark Ocean
journal, September 2011


sinI- and expR-Dependent Quorum Sensing in Sinorhizobium meliloti
journal, November 2005


Phylogenomic Data Support a Seventh Order of Methylotrophic Methanogens and Provide Insights into the Evolution of Methanogenesis
journal, August 2013

  • Borrel, Guillaume; O’Toole, Paul W.; Harris, Hugh M. B.
  • Genome Biology and Evolution, Vol. 5, Issue 10
  • DOI: 10.1093/gbe/evt128

Formation and breakdown of glycine betaine and trimethylamine in hypersaline environments
journal, November 1990


A proteomic determination of cold adaptation in the Antarctic archaeon, Methanococcoides burtonii: Cold adaptation on an Antarctic archaeon
journal, May 2004


Glycine reductase mechanism
journal, October 2004


The Sinorhizobium meliloti Glycine Betaine Biosynthetic Genes ( betICBA ) Are Induced by Choline and Highly Expressed in Bacteroids
journal, August 2003

  • Mandon, Karine; Østerås, Magne; Boncompagni, Eric
  • Molecular Plant-Microbe Interactions, Vol. 16, Issue 8
  • DOI: 10.1094/MPMI.2003.16.8.709

Bacterioplankton assemblages transforming dissolved organic compounds in coastal seawater
journal, August 2007


The BCCT family of carriers: from physiology to crystal structure: BCCT carriers
journal, September 2010


Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk
journal, April 2013

  • Tang, W. H. Wilson; Wang, Zeneng; Levison, Bruce S.
  • New England Journal of Medicine, Vol. 368, Issue 17
  • DOI: 10.1056/NEJMoa1109400

An Improved General Amino Acid Replacement Matrix
journal, April 2008


Basic Local Alignment Search Tool
journal, October 1990


Isolation of two novel corrinoid proteins from acetate-grown Methanosarcina barkeri.
journal, August 1993


Interrelations between Glycine Betaine Catabolism and Methionine Biosynthesis in Sinorhizobium meliloti Strain 102F34
journal, October 2006

  • Barra, L.; Fontenelle, C.; Ermel, G.
  • Journal of Bacteriology, Vol. 188, Issue 20
  • DOI: 10.1128/JB.00208-06

Kinetic and structural features of betaine aldehyde dehydrogenases: Mechanistic and regulatory implications
journal, January 2010

  • Muñoz-Clares, Rosario A.; Díaz-Sánchez, Ángel G.; González-Segura, Lilian
  • Archives of Biochemistry and Biophysics, Vol. 493, Issue 1
  • DOI: 10.1016/j.abb.2009.09.006

Carnitine--metabolism and functions
journal, October 1983


Archaebiotics: Proposed therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease
journal, October 2013

  • Brugère, Jean-François; Borrel, Guillaume; Gaci, Nadia
  • Gut Microbes, Vol. 5, Issue 1
  • DOI: 10.4161/gmic.26749

GbdR Regulates Pseudomonas aeruginosa plcH and pchP Transcription in Response to Choline Catabolites
journal, December 2008

  • Wargo, M. J.; Ho, T. C.; Gross, M. J.
  • Infection and Immunity, Vol. 77, Issue 3
  • DOI: 10.1128/IAI.01008-08

The Desulfitobacterium genus
journal, September 2006


Molecular mechanisms underlying roseobacter–phytoplankton symbioses
journal, June 2010


Uptake of glycine betaine and its analogues by bacteroids of Rhizobium meliloti
journal, January 1990


Genome characteristics of a generalist marine bacterial lineage
journal, January 2010

  • Newton, Ryan J.; Griffin, Laura E.; Bowles, Kathy M.
  • The ISME Journal, Vol. 4, Issue 6
  • DOI: 10.1038/ismej.2009.150

One Carbon Metabolism in SAR11 Pelagic Marine Bacteria
journal, August 2011


The Residue Mass of L-Pyrrolysine in Three Distinct Methylamine Methyltransferases
journal, August 2005

  • Soares, Jitesh A.; Zhang, Liwen; Pitsch, Rhonda L.
  • Journal of Biological Chemistry, Vol. 280, Issue 44
  • DOI: 10.1074/jbc.M506402200

Reactivity and Chemical Synthesis of L-Pyrrolysine— the 22nd Genetically Encoded Amino Acid
journal, September 2004


Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
journal, April 2011

  • Wang, Zeneng; Klipfell, Elizabeth; Bennett, Brian J.
  • Nature, Vol. 472, Issue 7341
  • DOI: 10.1038/nature09922

Glycine Betaine as a Direct Substrate for Methanogens (Methanococcoides spp.)
journal, October 2013

  • Watkins, Andrew J.; Roussel, Erwan G.; Parkes, R. John
  • Applied and Environmental Microbiology, Vol. 80, Issue 1
  • DOI: 10.1128/AEM.03076-13

Functional context, biosynthesis, and genetic encoding of pyrrolysine
journal, June 2011

  • Gaston, Marsha A.; Jiang, Ruisheng; Krzycki, Joseph A.
  • Current Opinion in Microbiology, Vol. 14, Issue 3
  • DOI: 10.1016/j.mib.2011.04.001

Regulation of homocysteine metabolism and methylation in human and mouse tissues
journal, August 2010

  • Chen, Natalie C.; Yang, Fan; Capecci, Louis M.
  • The FASEB Journal, Vol. 24, Issue 8
  • DOI: 10.1096/fj.09-143651

Novel pathway for assimilation of dimethylsulphoniopropionate widespread in marine bacteria
journal, May 2011

  • Reisch, Chris R.; Stoudemayer, Melissa J.; Varaljay, Vanessa A.
  • Nature, Vol. 473, Issue 7346
  • DOI: 10.1038/nature10078

Osmotic control of glycine betaine biosynthesis and degradation in Rhizobium meliloti.
journal, July 1988


Identification of Two Gene Clusters and a Transcriptional Regulator Required for Pseudomonas aeruginosa Glycine Betaine Catabolism
journal, October 2007

  • Wargo, M. J.; Szwergold, B. S.; Hogan, D. A.
  • Journal of Bacteriology, Vol. 190, Issue 8
  • DOI: 10.1128/JB.01393-07

Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis
journal, May 2020


Production of glycine betaine and dimethylsulfoniopropionate in marine phytoplankton. I. Batch cultures
journal, November 1999

  • Keller, M. D.; Kiene, R. P.; Matrai, P. A.
  • Marine Biology, Vol. 135, Issue 2
  • DOI: 10.1007/s002270050621

A rare SAR11 fosmid clone confirming genetic variability in the ‘Candidatus Pelagibacter ubique’ genome
journal, May 2008

  • Gilbert, Jack A.; Mühling, Martin; Joint, Ian
  • The ISME Journal, Vol. 2, Issue 7
  • DOI: 10.1038/ismej.2008.49

Organization of the genes involved in dimethylglycine and sarcosine degradation in Arthrobacter spp. : Implications for glycine betaine catabolism
journal, June 2001


MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0
journal, October 2013

  • Tamura, Koichiro; Stecher, Glen; Peterson, Daniel
  • Molecular Biology and Evolution, Vol. 30, Issue 12
  • DOI: 10.1093/molbev/mst197

Characterization of a Three-Component Vanillate O-Demethylase from Moorella thermoacetica
journal, June 2001


Formation of N,N-Dimethylglycine, Acetic Acid, and Butyric Acid from Betaine by Eubacterium limosum
journal, January 1981


Basic local alignment search tool
journal, October 1990

  • Altschul, Stephen F.; Gish, Warren; Miller, Webb
  • Journal of Molecular Biology, Vol. 215, Issue 3, p. 403-410
  • DOI: 10.1016/S0022-2836(05)80360-2

Works referencing / citing this record:

Trimethylamine-N-oxide and its biological variations in vegetarians
journal, August 2016

  • Obeid, Rima; Awwad, Hussain M.; Keller, Markus
  • European Journal of Nutrition, Vol. 56, Issue 8
  • DOI: 10.1007/s00394-016-1295-9

Structures in Tetrahydrofolate Methylation in Desulfitobacterial Glycine Betaine Metabolism at Atomic Resolution
journal, November 2019


Chemical transformation of xenobiotics by the human gut microbiota
journal, June 2017


A new family of uncultivated bacteria involved in methanogenesis from the ubiquitous osmolyte glycine betaine in coastal saltmarsh sediments
journal, August 2019


Phylogeography, Salinity Adaptations and Metabolic Potential of the Candidate Division KB1 Bacteria Based on a Partial Single Cell Genome
text, January 2015

  • M., Nigro, Lisa; S., Hyde, Andrew; Andreas, Teske,
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/v3va-mn98

A new family of uncultivated bacteria involved in methanogenesis from the ubiquitous osmolyte glycine betaine in coastal saltmarsh sediments
journal, August 2019


Viral and metabolic controls on high rates of microbial sulfur and carbon cycling in wetland ecosystems
journal, August 2018


Deltaproteobacteria (Pelobacter) and Methanococcoides are responsible for choline-dependent methanogenesis in a coastal saltmarsh sediment
journal, September 2018


Comparative genomics and physiology of the genus Methanohalophilus , a prevalent methanogen in hydraulically fractured shale
journal, December 2018

  • Borton, Mikayla A.; Daly, Rebecca A.; O'Banion, Bridget
  • Environmental Microbiology, Vol. 20, Issue 12
  • DOI: 10.1111/1462-2920.14467

Pyrrolysine in archaea: a 22nd amino acid encoded through a genetic code expansion
journal, November 2018

  • Brugère, Jean-François; Atkins, John F.; O'Toole, Paul W.
  • Emerging Topics in Life Sciences, Vol. 2, Issue 4
  • DOI: 10.1042/etls20180094

Viral and metabolic controls on high rates of microbial sulfur and carbon cycling in wetland ecosystems
journal, August 2018


Pyrrolysine in archaea: a 22nd amino acid encoded through a genetic code expansion
journal, November 2018

  • Brugère, Jean-François; Atkins, John F.; O'Toole, Paul W.
  • Emerging Topics in Life Sciences, Vol. 2, Issue 4
  • DOI: 10.1042/etls20180094

Isolation and characterization of a tetramethylammonium-degrading Methanococcoides strain and a novel glycine betaine-utilizing Methanolobus strain
journal, October 2014

  • Ticak, Tomislav; Hariraju, Dinesh; Arcelay, Margarette Bayron
  • Archives of Microbiology, Vol. 197, Issue 2
  • DOI: 10.1007/s00203-014-1043-6

Biochemical characterization of the methylmercaptopropionate:cob(I)alamin methyltransferase from Methanosarcina acetivorans
journal, February 2019

  • Fu, He; Goettge, Michelle N.; Metcalf, William W.
  • Journal of Bacteriology
  • DOI: 10.1101/548461

Coupled laboratory and field investigations resolve microbial interactions that underpin persistence in hydraulically fractured shales
journal, June 2018

  • Borton, Mikayla A.; Hoyt, David W.; Roux, Simon
  • Proceedings of the National Academy of Sciences, Vol. 115, Issue 28
  • DOI: 10.1073/pnas.1800155115

Chemical transformation of xenobiotics by the human gut microbiota
journal, June 2017


Whole genome sequencing of a novel, dichloromethane-fermenting Peptococcaceae from an enrichment culture
journal, January 2019

  • Holland, Sophie I.; Edwards, Richard J.; Ertan, Haluk
  • PeerJ, Vol. 7
  • DOI: 10.7717/peerj.7775

The Role of Gut Microbiota and Diet on Uremic Retention Solutes Production in the Context of Chronic Kidney Disease
journal, April 2018


Glycine betaine metabolism in the acetogenic bacterium Acetobacterium woodii
journal, October 2018

  • Lechtenfeld, Mats; Heine, Julia; Sameith, Janin
  • Environmental Microbiology, Vol. 20, Issue 12
  • DOI: 10.1111/1462-2920.14389

The metabolism and biotechnological application of betaine in microorganism
journal, March 2016

  • Zou, Huibin; Chen, Ningning; Shi, Mengxun
  • Applied Microbiology and Biotechnology, Vol. 100, Issue 9
  • DOI: 10.1007/s00253-016-7462-3

The Role of Gut Microbiota and Diet on Uremic Retention Solutes Production in the Context of Chronic Kidney Disease
journal, April 2018