title: Metabolite profiling and integrative modeling reveal metabolic constraints for carbon partitioning under nitrogen starvation in the green algae Haematococcus pluvialis.
abstract: The green alga Hematococcus 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 has been 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 hypotheses 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.
authors.affiliation: French Associates Institute for Agriculture and Biotechnology, the Jacob Blaustein Institutes for Desert Research, Ben Gurion University of the Negev, Sede Boker 84990, Israel.
authors.forename: Lee
authors.initials: L
authors.lastname: Recht
authors.affiliation: Systems Biology and Mathematical Modeling Group, Max Planck Institute of Molecular Plant Physiology, Potsdam 14476, Germany, and.
authors.forename: Nadine
authors.initials: N
authors.lastname: Töpfer
authors.affiliation: French Associates Institute for Agriculture and Biotechnology, the Jacob Blaustein Institutes for Desert Research, Ben Gurion University of the Negev, Sede Boker 84990, Israel.
authors.forename: Albert
authors.initials: A
authors.lastname: Batushansky
authors.affiliation: French Associates Institute for Agriculture and Biotechnology, the Jacob Blaustein Institutes for Desert Research, Ben Gurion University of the Negev, Sede Boker 84990, Israel.
authors.forename: Noga
authors.initials: N
authors.lastname: Sikron
authors.affiliation: INRA, Université de Bordeaux, Bordeaux Metabolome Facility Bordeaux, UMR 1332 Fruit Biology and Pathology, Villenave d'Ornon 33140, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Gibon
authors.affiliation: French Associates Institute for Agriculture and Biotechnology, the Jacob Blaustein Institutes for Desert Research, Ben Gurion University of the Negev, Sede Boker 84990, Israel.
authors.forename: Aaron
authors.initials: A
authors.lastname: Fait
authors.affiliation: Systems Biology and Mathematical Modeling Group, Max Planck Institute of Molecular Plant Physiology, Potsdam 14476, Germany, and.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Nikoloski
authors.affiliation: French Associates Institute for Agriculture and Biotechnology, the Jacob Blaustein Institutes for Desert Research, Ben Gurion University of the Negev, Sede Boker 84990, Israel,. Electronic address: sammy@bgu.ac.il.
authors.forename: Sammy
authors.initials: S
authors.lastname: Boussiba
authors.affiliation: French Associates Institute for Agriculture and Biotechnology, the Jacob Blaustein Institutes for Desert Research, Ben Gurion University of the Negev, Sede Boker 84990, Israel.
authors.forename: Aliza
authors.initials: A
authors.lastname: Zarka
mesh_terms: D050260:Carbohydrate Metabolism; D002338:Carotenoids / Q000378:metabolism; D000460:Chlorophyta / Q000378:metabolism* / Q000528:radiation effects; D002952:Citric Acid Cycle; D016000:Cluster Analysis; D003198:Computer Simulation; D005227:Fatty Acids / Q000096:biosynthesis; D008027:Light; D064688:Metabolic Flux Analysis; D055442:Metabolome; D009584:Nitrogen / Q000378:metabolism*; D013213:Starch / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D005227:Fatty Acids; D002338:Carotenoids; D013213:Starch; D009584:Nitrogen
keywords: Algae; Carbohydrate Metabolism; Computational Biology; Constraint-based Modeling; Data Integration; Fatty Acid Metabolism; Haematococcus pluvialis; Metabolomics; Nitrogen Starvation; Systems Biology