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Multi-Omics Reveals Temporal Scales of Carbon Metabolism in Synechococcus Elongatus PCC 7942 Under Light Disturbance

Connah G. M. Johnson1,*, Zachary Johnson2,3,*, Liam S. Mackey4,*, Xiaolu Li2, Natalie C. Sadler2, Tong Zhang2, Wei-Jun Qian2, Pavlo Bohutskyi2,3, Song Feng2,† et al.

Margaret S. Cheung2,5,6,‡

  • *These authors contributed equally to this work.
  • †Contact author: song.feng@pnnl.gov
  • ‡Contact author: margaret.cheung@pnnl.gov
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PRX Life 3, 033017 – Published 2 September, 2025

DOI: https://doi.org/10.1103/l2dp-kw2t

Abstract

Central carbon metabolism in model cyanobacteria involves multiple pathways to adapt to energy-light limitations across diel cycles. However, the success in mechanistic modeling for phenotypic prediction of the protein regulators in the metabolic state depends on capturing the vast possibilities emerging from multiple regulatory pathways in complex biological processes. Here, we developed a physics-informed machine learning approach based on energy-landscape concepts to predict regulatory proteins responding to cyclic circadian and unforeseen light perturbations in cyanobacterial metabolic networks. Our approach provides interpretable de novo models for inferring gene expression dynamics from Synechococcus elongatus over diel cycles and using redox proteome analysis to distinguish immediate light-responsive elements from circadian-regulated processes in carbon metabolism pathways. We identified distinct temporal signatures with the analysis of the redox proteome: there was an immediate shift in cysteine redox states accompanied by a limited change in protein abundance under constant illumination and after 2 hours of darkness. This discovery indicates that the generation of reductants coordinates photoinduced electron transport with redox metabolic pathways in two discernable molecular mechanisms: fast redox-based protein modifications occur immediately after the light disturbance, followed by slow transcriptional regulations across networks. This temporal regulation reveals how metabolic networks integrate rapid light responses with programmed circadian rhythms to maintain cellular homeostasis under the light-energy limitations over the diel cycle.

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PRX Life 3, 033017– Published 2 September, 2025
  • Received 23 January 2025
  • Accepted 30 July 2025
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Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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