Biomolecular Condensates Power Nitrogen Cycling via Concurrent Redox Activities

The role of the inherent chemical activities of biomolecular condensates in metabolism remains underexplored. We discovered that biomolecular condensates, the constituents of which do not possess any intrinsic enzymatic activities, can modulate the nitrogen cycle composed of nitrate (NO₃^-), ammonia (NH₃), and nitric oxide (NO·). By developing a single-condensate-based mass spectrometry technique, we observed condensate-dependent interconversion between NO₃^- and NH₄⁺ with externally supplied nitrogen sources. Surprisingly, through mass-spectrometry-based protein analysis and fluorogenic reaction assays, we found that the autoxidation of the arginine residue on the disordered protein could also directly contribute to the released NO·, an important signaling factor in biological systems. This work expands our understanding about the intrinsic reactivity of biomolecular condensates, providing insight into its fundamental impact on nitrogen metabolism as a nitrogen supplier and regulator.