Cells use various signaling molecules to regulate the nervous, immune, and vascular systems. Among these, nitric oxide (NO) and ammonia (NH₃) play important roles, but their chemical instability and gaseous nature make them difficult to generate or control externally. A KAIST research team has developed a platform that generates specific signaling molecules in situ from a single precursor under an applied electrical signal, enabling switch-like, precise spatiotemporal control of cellular responses. This approach could provide a foundation for future medical technologies such as electroceuticals, electrogenetics, and personalized cell therapies.

KAIST (President Kwang Hyung Lee) announced on August 11 that a research team led by Professor Jimin Park from the Department of Chemical and Biomolecular Engineering, in collaboration with Professor Jihan Kim's group, has developed a 'Bioelectrosynthesis Platform' capable of producing either nitric oxide or ammonia on demand using only an electrical signal. The platform allows control over the timing, spatial range, and duration of cell responses.

Inspired by enzymes involved in nitrite reduction, the researchers implemented an electrochemical strategy that selectively produces nitric oxide or ammonia from a single precursor, nitrite (NO₂^⁻). By changing the catalyst, the team generated ammonia or nitric oxide from nitrite using a copper-molybdenum-sulfur catalyst (Cu₂MoS₄) and an iron-incorporated catalyst (FeCuMS₄), respectively.

Through electrochemical measurements and computer simulations, the team revealed that Fe sites in the FeCuMoS₄ catalyst bind nitric oxide intermediates more strongly, shifting product selectivity toward nitric oxide. Under the same electrical conditions, the Fe-containing catalyst preferentially produces nitric oxide, whereas the Cu₂MoS₄ catalyst favors ammonia production.
The research team demonstrated biological functionality by using the platform to activate ion channels in human cells. Specifically, electrochemically produced nitric oxide activated TRPV1 channels (responsive to heat and chemical stimuli), while electrochemically produced ammonia induced intracellular alkalinization and activated OTOP1 proton channels. By tuning the applied voltage and electrolysis duration, the team modulated the onset time, spatial extent, and termination of cellular responses, which effectively turned cellular signaling on and off like a switch.

Professor Jimin Park said, "This work is significant because it enables precise cellular control by selectively producing signaling molecules with electricity. We believe it has strong potential for applications in electroceutical technologies targeting the nervous system or metabolic disorders."

Myeongeun Lee and Jaewoong Lee, Ph.D. students in the Department of Chemical and Biomolecular Engineering at KAIST, served as the co-first authors. Professor Jihan Kim is a co-author. The paper was published online in 'Angewandte Chemie International Edition' on July 8, 2025 (DOI: 10.1002/ange.202508192).

Reference: https://doi.org/10.1002/ange.202508192

Authors: Myeongeun Lee†, Jaewoong Lee†, Yongha Kim, Changho Lee, Sang Yeon Oh, Prof. Jihan Kim, Prof. Jimin Park^*

^†These authors contributed equally. ^*Corresponding author.