Metabolite Profiling and Integrative Modeling Reveal Metabolic Constraints for Carbon Partitioning under Nitrogen-Starvation in the Green Alga Haematococcus pluvialis.

The green alga Haematococcus pluvialis accumulates large amounts of the antioxidant astaxanthin under inductive stress conditions, such as nitrogen starvation. The response to nitrogen starvation and high-light leads to the accumulation of carbohydrates and fatty acids, as well as increased activity of the tricarboxylic acid cycle. Although the behavior of individual pathways is well-investigated, little is known about the systemic effects of the stress-response mechanism. Here we present time-resolved metabolite, enzyme activity, and physiological data that capture the metabolic response of H. pluvialis under nitrogen starvation and high-light. The data were integrated into a putative genome-scale model of the green alga to in silico test the hypothesis of underlying carbon partitioning. The model-based hypothesis testing reinforces the involvement of starch degradation to support fatty acid synthesis in the later stages of the stress response. In addition, our findings support a possible mechanism for the involvement of the increased activity of the tricarboxylic acid cycle in carbon repartitioning. Finally, the in vitro experiments and the in silico modeling presented here emphasize the predictive power of large-scale integrative approaches to pinpoint metabolic adjustment to changing environments