New way to produce nitric oxide on-demand

Researchers from Jiangsu University, Suzhou Industrial Park Xinghu Hospital, and Baicheng Normal University have mapped the diversity of natural nitrite-reducing enzymes and cataloged a new generation of artificial mimics that can convert nitrite into useful products—most notably nitric oxide and ammonia—under conditions relevant to medicine, food safety, and environmental protection. By overcoming the instability and high cost of natural enzymes, these synthetic catalysts promise on-demand nitric oxide release for cardiovascular and antibacterial therapies, sensitive nitrite sensing, and more environmentally friendly ammonia production.

Nitrite Reduction Drives Medicine, Diagnostics & Green Ammonia

Nitrite reduction underpins blood-pressure regulation, tissue oxygenation, and microbial nitrogen cycling. Harnessing this chemistry could yield low-cost supplements for hypertension or ischemia, precise antibiofilm treatments to combat antibiotic resistance, and rapid sensors for oral health and cellular diagnostics. In agriculture and industry, artificial nitrite reductases (NiR) provide energy-saving pathways for synthesizing ammonia, thereby reducing reliance on traditional high-temperature processes.

From Natural Enzymes to Synthetic Mimics: Key Discoveries

From the compiled data, several significant findings emerge:

• Enzyme families defined. Natural NiRs fall into two groups: one-electron enzymes that produce nitric oxide (e.g., copper and heme proteins) and six-electron enzymes that make ammonia (e.g., multiheme and siroheme-containing proteins).
• Artificial mimics developed. Researchers have designed de novo peptides, reverse-engineered multi-domain proteins, metal–azacycle and porphyrin complexes, metal-organic frameworks, biohybrid nanoparticles, and single-atom catalysts that replicate NiR activity across diverse materials.
• Biomedical applications. Engineered nanozymes deliver nitric oxide electrochemically or thermally to kill bacteria, disrupt biofilms, and promote wound healing. At the same time, biosensors built from natural or mimicked enzymes detect nitrite and nitric oxide in saliva and live cells with high sensitivity.
• Catalytic performance. Some single-atom and MOF-based mimics achieve over 90% efficiency for nitrite-to-nitric oxide conversion, with sustained release profiles suitable for week-long medical coatings. Meanwhile, ammonia-making mimics exhibit near-perfect selectivity under mild conditions.

“Our survey highlights over a dozen new catalyst designs, each tailored to overcome the cost and stability challenges of traditional enzymes,” Prof. Yonghai Feng explained. “This diversity gives us a toolbox for targeted applications.”

Structural & Computational Insights Guide Catalyst Design

The authors performed a comprehensive literature survey, integrating structural data from X-ray crystallography, cryo-EM, and time-resolved spectroscopies with computational studies to elucidate how metal coordination, surrounding protein residues, and proton-relay networks drive catalysis. They then reviewed synthetic strategies—protein engineering, coordination chemistry, nanofabrication, and material immobilization—used to create and test nitrite reductase mimics in standardized catalytic and electrochemical assays.

Roadmap to Next-Gen Nitrite-Reducing Catalysts

By integrating mechanistic insights with materials innovation, this review outlines a roadmap for next-generation nitrite reductase mimics that strike a balance between enzyme-level activity, stability in complex media, and tunable selectivity. Published in Research in May 2025 (DOI: https://doi.org/10.34133/research.0710), this work lays the groundwork for future studies to couple ultrafast structural techniques, supramolecular design, and stimuli-responsive platforms, thereby advancing both fundamental biology and real-world applications.

Sources: https://doi.org/10.34133/research.0710