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Single-cell metabolic flux analysis reveals coexisting optimal sub-groups, cross-feeding, and mixotrophy in a cyanobacterial population

2025/06/06 by Arián Ferrero-Fernández, Ferrero-Fernández, Arián, Paula Prondzinsky +13
Engineering · Agricultural and Biological Sciences · Environmental Science · #Ion-surface interactions and analysis #Biocrusts and Microbial Ecology #Aquatic Ecosystems and Phytoplankton Dynamics

paper · pdf · doi:10.48550/arxiv.2506.05916

Abstract

We derive a single-cell level understanding of metabolism in an isogenic cyanobacterial population by integrating secondary ion mass spectrometry (SIMS) derived multi-isotope uptake measurements of Synechocystis sp. PCC6803 with a statistical inference protocol based on Liebig's law of the minimum, the maximum entropy principle, and constraint-based modeling. We find the population is structured in two metabolically distinct clusters: cells optimizing carbon yield while excessively turning over nitrogen, and cells which act reciprocally, optimizing nitrogen yield and excessively turning over carbon. This partition enables partial heterotrophy within the population via metabolic exchange, likely in the form of organic acids. Exchange increases the feasible metabolic space, and mixotrophic cells achieve the fastest growth rates. Metabolic flux analysis at the single-cell level reveals heterogeneity in carbon fixation rates, Rubisco specificity, and nitrogen assimilation. Our results provide a necessary foundation for understanding how population level phenotypes arise from the collective contributions of distinct individuals.

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