A new framework for metabolic modeling under non-balanced growth. Application to carbon metabolism of unicellular microalgae

Macroscopic and metabolic models are ubiquitous tools for bioprocess modeling and understanding. While these two modeling approaches bring answers to different objectives, a remaining challenging question is how to couple macroscopic and intracellular models to enlarge the prediction capabilities of the model while keeping a model structure with low complexity level? In this paper, we provide conceptual guidelines to address this question. We propose a new modeling framework that manages non-balanced growth condition and hence accumulation of intracellular metabolites. The first stage consists in determining metabolic sub-networks, which are assumed to satisfy balanced growth condition. Then, the remaining metabolites interconnecting the sub-networks can dynamically accumulate or be reused. The basis of our approach is illustrated for the carbon metabolic network of unicellular microalgae.