Drug discovery-based approach identifies improved nitrification inhibitors

Abstract Nitrogen (N) fertilization is crucial to sustain global food security, but fertilizer N production is energy-demanding and subsequent environmental N losses contribute to biodiversity loss and climate change. To mitigate the environmental impact of N-fertilizers, nitrification inhibitors can be applied to produce so-called enhanced efficiency fertilizers (EEFs), which effectively reduce nitrogen pollution. However, current nitrification inhibitors have limitations and do not target all nitrifying microorganisms. Hence, to identify broad-spectrum nitrification inhibitors, we adopted a drug discovery-based approach and screened 45,400 small molecules on different groups of nitrifying microorganisms. Although a high number of potential nitrification inhibitors were identified, none of them targeted all nitrifier groups. However, co-applying different types of inhibitors resulted in a synergistic effect, both in the reduction of ammonium consumption and greenhouse gas emissions, beyond what is achieved with currently applied nitrification inhibitors. This advocates for combining different types of nitrification inhibitors in EEFs to render agriculture more sustainable.