Bioelectrosynthesis of Signaling Molecules for Selective Modulation of Cell Signaling

Bioelectrosynthesis holds great potential for studying and regulating biological systems through the in situ synthesis and delivery of cell signaling molecules with high spatiotemporal precision. Despite recent advancements, precise control over multiple signaling molecules within a single platform remains challenging. Here, we introduce a bioelectrosynthesis approach capable of selectively producing two types of signaling molecules from a single precursor. This system leverages multi-metal sulfide electrocatalysts inspired by denitrifying enzymes, which generate signaling molecules, nitric oxide (NO), and ammonia (NH₃) from nitrite ions. By controlling catalytic active sites, NO or NH₃ can be selectively produced under mild electric fields in physiologically relevant conditions. In situ product analyses and first-principles calculations reveal that NO intermediate binding affinity determines product selectivity. These electrocatalysts integrate seamlessly with biological systems, allowing precise, on-demand modulation of NO- or NH₃-mediated signaling pathways in human cell lines. By combining electrochemical precision with selective cell control, this strategy may advance the study and regulation of biological systems.