Natural Rhythms Boost Product Synthesis in Sleep-Deprived Cyanobacteria

The Science

Scientists have discovered that cyanobacteria's internal clock can dramatically improve their ability to convert carbon dioxide (CO₂) into valuable products. These microscopic organisms, which normally photosynthesize during the day and rest at night, showed surprising behavior when kept in constant light. 

During the nighttime, when they expected darkness but were kept in light, the bacteria produced three times more sucrose than when they were in the light during the daytime, even though their photosynthesis genes were less active. This enhanced production happened because their internal clock redirected carbon flow, breaking down stored energy reserves while halting competing processes like cell division. This discovery, part of Pacific Northwest National Laboratory's Predictive Phenomics Initiative offers fundamental insights into how cellular timekeeping creates distinct windows that favor either growth or production, suggesting new strategies for sustainable biomanufacturing.

The Impact

This research provides significant insights into how circadian rhythms control carbon partitioning between growth, storage, and product formation in cyanobacteria. The discovery that cellular timekeeping creates distinct metabolic states with dramatic impact on bioproduction represents an important advance in our understanding of bacterial metabolism and its regulation. By revealing how networks of genes coordinate to optimize resource allocation, this work helps resolve key questions about temporal separation of competing cellular processes. The findings are particularly valuable as they demonstrate that enhanced production can occur even when photosynthetic machinery is down-regulated, challenging previous assumptions about bioproduction optimization. These insights open promising new approaches for improving CO₂-to-product conversion, either by timing production to align with natural rhythms or by engineering strains that mimic beneficial nighttime metabolic states. 

Summary

The study revealed how cyanobacteria's circadian clock orchestrates complex cellular processes to enhance bioproduction. During subjective night, these organisms showed coordinated changes in over 300 genes, rewiring their metabolism to favor product formation over growth and storage. The clock regulated key processes, including photosynthesis, carbon storage, cell division, and electron transport. This temporal separation created optimal conditions for sucrose production by increasing the availability of precursor molecules while maintaining cellular energy balance through multiple mechanisms. The research suggests that either leveraging natural rhythms or engineering strains to mimic beneficial nighttime states could improve industrial bioproduction. These findings emerged from comprehensive analysis combining production measurements, cellular imaging, and genome-wide gene expression studies, providing detailed insights into how cellular timekeeping affects metabolism and bioproduction.

Contact

• Pavlo Bohutskyi, pavlo.bohutskyi@pnnl.gov, PNNL

Funding

The research described in this paper is part of the Predictive Phenomics Initiative and was conducted under the Laboratory Directed Research and Development Program at Pacific Northwest National Laboratory. This work is also partially supported by the NW-BRaVE for Biopreparedness project funded by the Department of Energy (DOE), Office of Science, Biological and Environmental Research program, under FWP 81832. A portion of this research was performed on a project award (https://doi.org/10.46936/staf.proj.2023.61054/60012367) from the Environmental Molecular Sciences Laboratory, a DOE Office of Science user facility at Pacific Northwest National Laboratory sponsored by the Biological and Environmental Research program (contract No. DE-AC05-76RL01830). Pacific Northwest National Laboratory is a multi-program national laboratory operated by Battelle for the DOE under Contract DE-AC05-76RLO 1830.