Transcriptome and Redox Proteome Reveal Temporal Scales of Carbon Metabolism Regulation in Model Cyanobacteria Under Light Disturbance

We develop a systems approach based on an energy-landscape concept to differentiate interactions involving redox activities and conformational changes of proteins and nucleic acids interactions in multi-layered protein-DNA regulatory networks under light disturbance. Our approach is a data-driven modeling workflow using a physics-informed machine learning algorithm to train a non-linear mathematical model for interpreting gene expression dynamics and to lead discovery for protein regulators using redox proteome analysis. We distinguish light-responsive elements within central carbon metabolism pathways from independent variables like circadian time using the publicly available transcriptome datasets of Synechococcus elongatus over diel cycles responding to light perturbations. Our approach provides interpretable de novo models for elucidating events of reactions in complex regulatory pathways in response to stressful disturbance from the environment. We discovered protein regulators in response to light disturbance in the proteome analysis involving shifts in protein abundance as well as cysteine redox states under constant illumination and after two hours of darkness. We discovered significant shifts in cysteine redox states in regulatory proteins such as transcription sigma factors and metabolic enzymes in the oxidative pentose phosphate pathway and the Calvin-Benson cycle, while the changes in their protein abundance were minimal. These results indicate that regulatory dynamics in reductant generation link photo-induced electron transport pathways and redox metabolic pathways with circadian rhythms through fast redox-induced conformational changes or slow expression regulations across networks.