1 research outputs found
Discovery of Fungal Denitrification Inhibitors by Targeting Copper Nitrite Reductase from <i>Fusarium oxysporum</i>
The efficient application of nitrogenous
fertilizers is urgently
required, as their excessive and inefficient use is causing substantial
economic loss and environmental pollution. A significant amount of
applied nitrogen in agricultural soils is lost as nitrous oxide (N<sub>2</sub>O) in the environment due to the microbial denitrification
process. The widely distributed fungus Fusarium oxysporum is a major denitrifier in agricultural soils and its denitrification
activity could be targeted to reduce nitrogen loss in the form of
N<sub>2</sub>O from agricultural soils. Here, we report the discovery
of first small molecule inhibitors of copper nitrite reductase (NirK)
from F. oxysporum, which is a key enzyme
in the fungal denitrification process. The inhibitors were discovered
by a hierarchical in silico screening approach consisting of pharmacophore
modeling and molecular docking. In vitro evaluation of F. oxysporum NirK activity revealed several pyrimidone
and triazinone based compounds with potency in the low micromolar
range. Some of these compounds suppressed the fungal denitrification
in vivo as well. The compounds reported here could be used as starting
points for the development of nitrogenous fertilizer supplements and
coatings as a means to prevent nitrogen loss by targeting fungal denitrification