Biological and nonthermal plasma methane activation to methanol: Mechanisms, challenges, and prospects for hybrid systems

• Proposes hybrid bio-plasma systems for sustainable methane utilization. • Reviews advances in biological and nonthermal plasma (NTP) activation of methane. • Summarizes activation mechanisms of methane monooxygenases (MMOs) • Explains radical-mediated pathways enabled by high-energy electrons in NTP systems. • Explores plasma-biocatalyst integration for higher selectivity and efficiency. Methane is both a valuable chemical feedstock and a potent greenhouse gas, and its selective valorization under mild conditions remains a key challenge for sustainable fuel and chemical production. Biological methane oxidation mediated by methane monooxygenases (MMOs) enables highly selective methane to methanol conversion at ambient conditions, but is constrained by gas–liquid mass transfer, reductant requirements, methanol overoxidation, and limited scalability. In contrast, NTP offers an electrified route for methane activation at low bulk temperatures, yet suffers from poor selectivity, high specific energy input, and reactor-scale efficiency limitations. This review critically compares the mechanistic foundations, performance characteristics, and system-level bottlenecks of biological and NTP-based methane activation routes. It examines how recent advances in plasma catalysis, reactor engineering, and enzyme-based methane oxidation influence selectivity, energy efficiency, and operational stability through catalyst design, discharge mode, and process configuration. On this basis, hybrid plasma-biological methane conversion is discussed as a process-level integration strategy, in which plasma and biocatalytic modules are functionally decoupled and strategically combined, rather than relying on direct radical-enzyme interactions. By integrating perspectives from microbiology, plasma science, catalysis, and process engineering, this work identifies critical bottlenecks and defines realistic research directions for developing hybrid methane to methanol systems with improved selectivity, energy efficiency, and scalability.