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Cited by 339Ruminant Nutrition and Digestive PhysiologyAnaerobic Digestion and Biogas ProductionAgriculture Sustainability and Environmental Impact

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 access
Duin, Evert C., Wagner, Tristan, Shima, Seigo, Prakash, Divya, Cronin, Bryan, Yáñez-Ruiz, David R., Duval, Stephane, Rümbeli, Robert, Stemmler, René T., Thauer, Rudolf Kurt, Kindermann, Maik·2016·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1600298113PMC PMC4896709
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Abstract

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.

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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
DOI
10.1073/pnas.1600298113
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
Licence
www.pnas.org/preview_site/misc/userlicense.xhtml (vor, 184 d)
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

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