The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol
Open accessAbstract
Ruminants, such as cows, sheep, and goats, predominantly ferment in their rumen plant material to acetate, propionate, butyrate, CO2, and methane. Whereas the short fatty acids are absorbed and metabolized by the animals, the greenhouse gas methane escapes via eructation and breathing of the animals into the atmosphere. Along with the methane, up to 12% of the gross energy content of the feedstock is lost. Therefore, our recent report has raised interest in 3-nitrooxypropanol (3-NOP), which when added to the feed of ruminants in milligram amounts persistently reduces enteric methane emissions from livestock without apparent negative side effects [Hristov AN, et al. (2015) Proc Natl Acad Sci USA 112(34):10663-10668]. We now show with the aid of in silico, in vitro, and in vivo experiments that 3-NOP specifically targets methyl-coenzyme M reductase (MCR). The nickel enzyme, which is only active when its Ni ion is in the +1 oxidation state, catalyzes the methane-forming step in the rumen fermentation. Molecular docking suggested that 3-NOP preferably binds into the active site of MCR in a pose that places its reducible nitrate group in electron transfer distance to Ni(I). With purified MCR, we found that 3-NOP indeed inactivates MCR at micromolar concentrations by oxidation of its active site Ni(I). Concomitantly, the nitrate ester is reduced to nitrite, which also inactivates MCR at micromolar concentrations by oxidation of Ni(I). Using pure cultures, 3-NOP is demonstrated to inhibit growth of methanogenic archaea at concentrations that do not affect the growth of nonmethanogenic bacteria in the rumen.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“This enzyme catalyzes the last step of methane-forming reactions (Duin et al., 2016) and its inhibition can result in a reduction in rumen methanogenesis (up to 30%) without negative effects to the animal (Hristov et al., 2015).”
From Addressing global ruminant agricultural challenges through understanding the rumen microbiome: past, present, and future (2018) · cites this paper as Duin et al., 2016
Citations
Cites
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
Climate Change 2007: The Physical Science Basis.
Schiavon, S., & Zecchin, R. (2007) · eScholarship (California Digital Library) · Cited by 16,994
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,796
Friesner, R. A., Banks, J. L., Murphy, R. B., Halgren, T. A., Klicic, J. J., Mainz, D. T., Repasky, M. P., Knoll, E. H., Shelley, M., Perry, J. K., et al. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm0306430 · Cited by 10,057
Friesner, R. A., Murphy, R. B., Repasky, M. P., Frye, L. L., Greenwood, J. R., Halgren, T. A., Sanschagrin, P. C., & Mainz, D. T. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm051256o · Cited by 7,012
Halgren, T. A., Murphy, R. B., Friesner, R. A., Beard, H. S., Frye, L. L., Pollard, W. T., & Banks, J. L. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm030644s · Cited by 5,340
MOLREP : an Automated Program for Molecular Replacement
Vagin, A. A., & Teplyakov, A. (1997) · Journal of Applied Crystallography · doi:10.1107/s0021889897006766 · Cited by 4,756
Energy conservation in chemotrophic anaerobic bacteria
Thauer, R. K., Jungermann, K., & Decker, K. (1977) · Bacteriological Reviews · doi:10.1128/br.41.1.100-180.1977 · Cited by 4,146
Self-citationiMOSFLM: a new graphical interface for diffraction-image processing withMOSFLM
Battye, T. G. G., Kontogiannis, L., Johnson, O., Powell, H. R., & Leslie, A. G. W. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910048675 · Cited by 2,880
Johnson, K. A., & Johnson, D. E. (1995) · Journal of Animal Science · doi:10.2527/1995.7382483x · Cited by 2,714 · cited 2×
“The generation of methane by methanogenic archaea in the intestine of domestic ruminants lessens feed efficacy, as up to 12% of the gross energy ingested by the animal is lost this way (7).”
Background
Cited by
Sorted by citations
Beauchemin, K. A., Ungerfeld, E. M., Eckard, R. J., & Wang, M. (2020) · Animal · doi:10.1017/s1751731119003100 · Cited by 619
Huws, S. A., Creevey, C. J., Oyama, L. B., Mizrahi, I., Denman, S. E., Popova, M., Muñoz-Tamayo, R., Forano, E., Waters, S. M., Hess, M., et al. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.02161 · Cited by 487
Rumen methanogens and mitigation of methane emission by anti-methanogenic compounds and substances
Patra, A. K., Park, T., Kim, M., & Yu, Z. (2017) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-017-0145-9 · Cited by 513
Metabolic Hydrogen Flows in Rumen Fermentation: Principles and Possibilities of Interventions
Ungerfeld, E. M. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00589 · Cited by 472
Roque, B. M., Venegas, M., Kinley, R. D., de Nys, R., Duarte, T. L., Yang, X., & Kebreab, E. (2021) · PLOS ONE · doi:10.1371/journal.pone.0247820 · Cited by 433
Metadata
- Authors
- Duin, E. C., Wagner, T., Shima, S., Prakash, D., Cronin, B., Yáñez-Ruiz, D. R., Duval, S., Rümbeli, R., Stemmler, R. T., Thauer, R. K., & Kindermann, M.
- Affiliations
- Auburn University (US)
- Max Planck Institute for Terrestrial Microbiology (DE)
- Estación Experimental del Zaidín, Consejo Superior de Investigaciones Cientificas, 18008 Granada, Spain;
- Research Centre for Animal Nutrition and Health, DSM Nutritional Products France, 68305 Saint Louis, France;
- Research and Development, DSM Nutritional Products, 4002 Basel, Switzerland
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-05-02
- Volume
- 113
- Issue
- 22
- Pages
- 6172-6177
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4896709
- OpenAlex
- W2345657234
- Cited by
- 339
- References
- 66
- Citations by year
- 2026: 44 · 2025: 59 · 2024: 56 · 2023: 40 · 2022: 40 · 2021: 30 · 2020: 18 · 2019: 25 · 2018: 14 · 2017: 8 · 2016: 5
- FWCI
- 35.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Max-Planck-Gesellschaft (no number)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Ruminant Nutrition and Digestive Physiology
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Anaerobic Digestion and Biogas Production
- Physical Sciences › Environmental Science › Ecology › Agriculture Sustainability and Environmental Impact
- Keywords
- 3-nitrooxypropanol, enteric methane, ruminants, methyl-coenzyme M reductase, rumen fermentation, methanogenesis inhibition, nickel enzymes, nitrate reduction, nitrite, methanogenic archaea, feed additives, greenhouse gas emissions reduction
- MeSH terms
- Animals, Methane, Oxidoreductases, Rumen, Ruminants, Euryarchaeota, Molecular Docking Simulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
