ArticleProceedings of the National Academy of Sciences of the United States of America2016
Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 130 papers, 1 of them a synthesis that pooled it.
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Who cites it
130 citing papers in PubMed, 1 synthesis or guideline pooled it, 323 citations in OpenAlex.
- A meta-analysis of effects of 3-nitrooxypropanol on methane production, yield, and intensity in dairy cattle.Journal of dairy science · 2023Pooled it
- Feed additives as frontline tools in mitigating greenhouse gas emissions from agricultural animals.Tropical animal health and production · 2026Review
- Comparative metataxonomic analysis of total, viable, and active rumen microbial communities under methane-mitigated conditions.Environmental microbiome · 2026Article
- Integrative analysis of rumen microbiota activity and host metabolism following methanogenesis inhibition in dairy cattle.Microbiology spectrum · 2026Article
- Nitro- and nitrooxy-organic inhibitors of methanogenesis: revealing knowledge gaps and alternate ways in bovine rumen microbiome metabolism.Applied and environmental microbiology · 2026Article
- Hypophosphite Is a Naturally Occurring Selective Inhibitor of Syntrophic Methanogenesis.Environmental science & technology · 2026Article
- Nutritional Strategies for Methane, Nitrogen, and Phosphorus Mitigation in Ruminants: Mechanisms, Applications, and Regional Adaptations.Microorganisms · 2026Review
- Chemical Characterization and Rumen-Modulating Effects ofMolecules (Basel, Switzerland) · 2026Article
- Proanthocyanidins inhibit methane emissions by interacting with methyl-coenzyme M reductase and reshaping rumen microbiome function.Microbiome · 2026Article
- Effects of coenzyme M and methyl-coenzyme M on the efficacy of inhibitors of methanogenesis in rumen cultures.Scientific reports · 2026Article
- Article
- Uncovering Major Structural and Functional Features of Methyl-Coenzyme M Reductase (MCR) fromInternational journal of molecular sciences · 2026Article
- Intracellular accumulation of hydrophobic 1,3-PDN inhibits methanogenesis in rumen methanogens.The ISME journal · 2026Article
- Biowaste-grown live microbial feed additive sustainably and significantly cut enteric methane emissions in Indian livestock.Scientific reports · 2026Article
- In vivo methane abatement by pyromellitic diimide in sheep and redirection of rumen hydrogen by co-administered feed additives.Journal of animal science · 2026Article
- Effect of two-doses of 3-nitrooxypropanol (3-NOP) on methane emissions, performance, rumen microbiome, and metabolomics in Nellore cattle.Journal of animal science · 2026Article
- Effects of 2-bromoethanesulfonate alone or in combination with calcium propionate or monensin on methane and gaseous hydrogen production during in vitro rumen fermentation.JDS communications · 2026Article
- Nitrate reduction salvage pathway inFrontiers in microbiology · 2026Article
- Dietary high-purity tribromoethanol (TBE) supplementation reduces enteric methane emissions in beef cattle.Translational animal science · 2026Article
- Investigating the antimethanogenic effects of selected nitro-compounds on methane production, rumen fermentation, and methanogenic archaeaApplied and environmental microbiology · 2025Article
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.