Efficient conversion of greenhouse gases into valuable products through methanotrophic fermentation requires optimization of gas transfer and process safety. This study presents a simulation-guided approach to enhance Methylococcus capsulatus (Bath) cultivation by combining predictive modeling with process intensification to maximize gas utilization while maintaining safe operating conditions. A simulation framework was developed to predict gas transfer rates across various oxygen/methane mixtures, enabling systematic optimization of operating conditions. Validation experiments in an ATEX-compliant pressure fermentation system (7.5 L reactor) confirmed the predicted transfer rates, with deviations below 3.1%. The model identified gas compositions that maximize transfer rates while remaining outside the explosive atmosphere range. Based on these results, the oxygen transfer rate (OTR) increased from 42.57 to 50.45 mmol/L/h (+18.5%) compared with the reference 50/50 methane/air condition at 0.1 bar(g). Safety during operation with flammable gases was ensured through real-time off-gas monitoring and automated shutdown systems, maintaining conditions outside the explosive range throughout fermentation. Dissolved-oxygen-tension-controlled aeration further improved gas conversion by matching gas supply to cellular demand. The developed system maintained high process reproducibility and enabled exploration of operating windows previously inaccessible due to ATEX constraints. Overall, this work demonstrates that predictive modeling combined with process intensification can improve both efficiency and safety in methanotrophic bioprocesses and provides a scalable strategy for greenhouse-gas conversion in sustainable biotechnology. • Computer models help design safer processes that feed methane to microbes. • Simulations predict gas transfer and explosion risk during methane fermentation. • Experiments confirm the model and show higher methane and oxygen use efficiency. • Pressure and smart aeration improve greenhouse gas conversion into biomass.
Engel et al. (Wed,) studied this question.