Nature Communications

Structure-guided identification of denitrification inhibitors to mitigate agricultural N2O emissions

2026-08-20

Reducing anthropogenic nitrous oxide emissions from agricultural lands is critical to combating climate change. Nitrification inhibitors and synthetic microbial consortia have already demonstrated potential in decreasing soil nitrification-derived nitrous oxide emissions. However, targeted interventions addressing denitrification sources while balancing agricultural sustainability remain challenging. Here, we identify triazole compounds as cytochrome P450 inhibitors capable of reducing soil denitrification-derived nitrous oxide emissions by 85-100% in laboratory settings. Extending our findings to in-situ paddy fields, we observe that triazoles (at 0.05% of fertilizer nitrogen) reduce nitrous oxide emissions by 33-54%. These potential inhibitors specifically target the NAD(P)H and nitric oxide binding sites of P450Nor, strongly inhibiting fungal nitrous oxide emissions. Occupancy of the heme-iron(III) site within the P450Nor active pocket enhances this selectivity, which is critical for effective inhibition. Given the projected increase in agricultural nitrous oxide emissions, our findings offer insights into the development of denitrification inhibitors and highlight triazole as a promising solution for nitrous oxide mitigation in agricultural ecosystems.

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DOI https://doi.org/10.1038/s41467-026-76975-6