An Exploratory Study on the Growth Dynamics of Alkalihalophilus marmarensis Using a Model-Based Approach

Alkalihalophilus marmarensis is an obligate alkaliphile with exceptional tolerance to high-pH environments, making it a promising candidate for industrial bioprocesses that require contamination-resistant and extremophilic production platforms. However, its practical deployment is hindered by limited biomass formation under extreme conditions, which constrains overall productivity. This study presents a model-driven investigation of how pH (8.8 and 10.5), culture duration (24 and 48 h), and nitrogen source composition (peptone and meat extract) affect cell dry mass, lactate, and protease synthesis. Using the response surface methodology and multi-objective optimization, we established predictive models (R2 up to 0.92) and uncovered key trade-offs in biomass and metabolite yields. Our findings reveal that peptone concentration critically shapes the metabolic output, with low levels inhibiting growth and high levels suppressing protease activity. Maximum cell dry mass (4.5 g/L), lactate (19.3 g/L), and protease activity (43.5 U/mL) were achieved under distinct conditions, highlighting the potential for targeted process tuning. While the model validation confirmed predictions for lactate, deviations in cell dry mass and protease outputs underscore the complexity of growth–product interdependencies under nutrient-limited regimes. This work delivers a foundational framework for developing fermentations with A. marmarensis and advancing its application in sustainable, high-pH industrial bioprocesses. The insights gained here can be further leveraged through synthetic biology and bioprocess engineering to fully exploit the metabolic potential of obligate alkaliphiles like A. marmarensis.