Machine Learning Optimization of Photosynthetic Microbe Cultivation and Recombinant Protein Production
Background: Arthrospira platensis (commonly known as spirulina) is a promising new platform for low-cost manufacturing of biopharmaceuticals. However, full realization of the platform's potential will depend on achieving both high growth rates of spirulina and high expression of therapeutic proteins. Objective: We aimed to optimize culture conditions for the spirulina-based production of therapeutic proteins. Methods: We used a machine learning approach called Bayesian black-box optimization to iteratively guide experiments in 96 photobioreactors that explored the relationship between production outcomes and 17 environmental variables such as pH, temperature, and light intensity. Results: Over 16 rounds of experiments, we identified key variable adjustments that approximately doubled spirulina-based production of heterologous proteins, improving volumetric productivity between 70% to 100% in multiple bioreactor setting configurations. Conclusion: An adaptive, machine learning-based approach to optimize heterologous protein production can improve outcomes based on complex, multivariate experiments, identifying beneficial variable combinations and adjustments that might not otherwise be discoverable within high-dimensional data.