Genome-Scale Metabolic Modeling to Study Interactions and Coevolution Between Cyanobacteria and Cyanophages
Authors:
Song Feng1* ([email protected]), Ruonan Wu1, Pavlo Bohutskyi1, Tong Zhang1, John Melchior1, Young-Mo Kim1, Xiaolu Li1, August George1, Youngki You1, Aaron Chan2, Zan Luthey-Schulten2, David D. Pollock1,3, Wei-Jun Qian1, Margaret S. Cheung1 (PI)
Institutions:
1Pacific Northwest National Laboratory; 2University of Colorado School of Medicine; 3University of Illinois Urbana-Champaign
Abstract
Marine cyanobacteria are well-known for their role in fixing nearly 30% of organic matter on Earth. Up to 60% of the cyanobacterial cells, however, are infected by phages. During phage infection, cyanobacterial metabolisms are reprogrammed towards phage replication, and the carbon dioxide (CO2) fixation functional module is inhibited via expressing phage auxiliary metabolic genes (AMGs). Such phenotypic change in primary producers is especially concerning given the impact of climate change. Moreover, different phages induce different host responses and life cycle changes that are likely driven by metabolic and molecular interaction network reprogramming.
Here, group members describe a genome-scale metabolic model of cyanobacteria combined with two additional biomass objective functions driving replication of two cyanophage strains, P-HM2 and P-SSP7. Using the dynamic flux balance analysis, the group will compare host-optimal solutions and phage-optimal solutions in the diurnal cycles with changing light intensities. Then the group will use this functional information of AMGs to compare the metabolic fluxes infected by different phage strains by enforcing AMG-associated reactions.
These analyses will reveal interactions between host and phages as well as metabolic reprogramming by cyanophages. Furthermore, this model will provide a basis for integrating multiomics data with a whole-cell systems model of cyanophage infection to better understand host-virus interactions. This research team will use the metabolic network as functional coordinates for enzymes. The abundance and state changes (e.g., post-translational modifications, conformational and interactional changes) can be mapped to the metabolic network model and whole-cell model to study their subsequent effects on phenotypes of cyanobacteria and/or cyanophages.