Development of a Chlamydomonas reinhardtii metabolic network dynamic model to describe distinct phenotypes occurring at different CO2 levels

The increase in atmospheric CO2 due to anthropogenic activities is generating climate change, which has resulted in a subsequent rise in global temperatures with severe environmental impacts. Biological mitigation has been considered as an alternative for environmental remediation and reduction of greenhouse gases in the atmosphere. In fact, the use of easily adapted photosynthetic organisms able to fix CO2 with low-cost operation is revealing its high potential for industry. Among those organism, the algae Chlamydomonas reinhardtii have gain special attention as a model organism for studying CO2 fixation, biomass accumulation and bioenergy production upon exposure to several environmental conditions. In the present study, we studied the Chlamydomonas response to different CO2 levels by comparing metabolomics and transcriptomics data with the predicted results from our new-improved genomic-scale metabolic model. For this, we used in silico methods at steady dynamic state varying the levels of CO2. Our main goal was to improve our capacity for predicting metabolic routes involved in biomass accumulation. The improved genomic-scale metabolic model presented in this study was shown to be phenotypically accurate, predictive, and a significant improvement over previously reported models. Our model consists of 3726 reactions and 2436 metabolites, and lacks any thermodynamically infeasible cycles. It was shown to be highly sensitive to environmental changes under both steady-state and dynamic conditions. As additional constraints, our dynamic model involved kinetic parameters associated with substrate consumption at different growth conditions (i.e., low CO2-heterotrophic and high CO2-mixotrophic). Our results suggest that cells growing at high CO2 (i.e., photoautotrophic and mixotrophic conditions) have an increased capability for biomass production. In addition, we have observed that ATP production also seems to be an important limiting factor for growth under the conditions tested. Our experimental data (metabolomics and transcriptomics) and the results predicted by our model clearly suggest a differential behavior between low CO2-heterotrophic and high CO2-mixotrophic growth conditions. The data presented in the current study contributes to better dissect the biological response of C. reinhardtii, as a dynamic entity, to environmental and genetic changes. These findings are of great interest given the biotechnological potential of this microalga for CO2 fixat