Kinetic and hybrid modeling for yeast astaxanthin production under uncertainty.

Astaxanthin is a high-value compound commercially synthesized through Xanthophyllomyces dendrorhous fermentation. Using mixed sugars decomposed from biowastes for yeast fermentation provides a promising option to improve process sustainability. However, little effort has been made to investigate the effects of multiple sugars on X. dendrorhous biomass growth and astaxanthin production. Furthermore, the construction of a high-fidelity model is challenging due to the system's variability, also known as batch-to-batch variation. Two innovations are proposed in this study to address these challenges. First, a kinetic model was developed to compare process kinetics between the single sugar (glucose) based and the mixed sugar (glucose and sucrose) based fermentation methods. Then, the kinetic model parameters were modeled themselves as Gaussian processes, a probabilistic machine learning technique, to improve the accuracy and robustness of model predictions. We conclude that although the presence of sucrose does not affect the biomass growth kinetics, it introduces a competitive inhibitory mechanism that enhances astaxanthin accumulation by inducing adverse environmental conditions such as osmotic gradients. Moreover, the hybrid model was able to greatly reduce model simulation error and was particularly robust to uncertainty propagation. This study suggests the advantage of mixed sugar-based fermentation and provides a novel approach for bioprocess dynamic modeling.