Hypophosphite is a naturally-occurring selective inhibitor of syntrophic methanogenesis
Microbial methanogenesis is a major contributor to global warming and methane fluxes represent a loss of energy and electrons from industrial ecosystems. The chemical space of methane control strategies is still under-explored. Most known methanogenesis inhibitors target methanogenic archaeal enzymes. However, interference with syntrophic electron exchange in methanogenic systems presents an additional target for methane control. Here we show that hypophosphite (H2PO2-), an inorganic formate analog, is a potent and selective inhibitor of syntrophic methanogenesis versus primary fermentation in rice field sediments and cattle rumens. Hypophosphite is also generally recognized as safe and relatively non-toxic to plants and animals. Genetic screens and physiological assays in the model methanogen Methanococcus maripaludis S2 implicate formate metabolism as the target of hypophosphite inhibition. Currently, there is no known biological pathway for anaerobic hypophosphite oxidation and hypophosphite is stable in anoxic sediments for weeks to months. Given its widespread natural occurrence, we propose that hypophosphite may modulate carbon cycling in natural environments. Taken together, our results suggest that hypophosphite could be used as a safe, inexpensive, strategy for methane control in syntrophic methanogenic ecosystems.