Biology subjects

Segre, D.

Publications and source records attributed to Segre, D..

39 records · Page 3Linked to original sources

bioRxiv2018

The thermodynamic landscape of carbon redox biochemistry

Redox biochemistry plays a key role in the transduction of chemical energy in living systems. However, the compounds observed in metabolic redox reactions are a minuscule fraction of chemical space. It is not clear whether compounds that ended up being selected as metabolites display specific properties that distinguish them from non-biological compounds. Here we introduce a systematic approach for comparing the chemical space of all possible redox states of linear-chain carbon molecules to the corresponding metabolites that appear in biology. Using cheminformatics and quantum chemistry, we analyze the physicochemical and thermodynamic properties of the biological and non-biological compounds. We find that, among all compounds, aldose sugars have the highest possible number of redox connections to other molecules. Metabolites are enriched in carboxylic acid functional groups and depleted of carbonyls, and have higher solubility than non-biological compounds. Upon constructing the energy landscape for the full chemical space as a function of pH and electron donor potential, we find that over a large range of conditions metabolites tend to have lower Gibbs energies than non-biological molecules. Finally, we generate Pourbaix phase diagrams that serve as a thermodynamic atlas to indicate which compounds are local and global energy minima in redox chemical space across a set of pH values and electron donor potentials. Our work yields insight into the physicochemical principles governing redox metabolism, and suggests that thermodynamic stability in aqueous environments may have played an important role in early metabolic processes.

systems biology↗

bioRxiv2017

Emergent Simplicity in Microbial Community Assembly

Microbes assemble into complex, dynamic, and species-rich communities that play critical roles in human health and in the environment. The complexity of natural environments and the large number of niches present in most habitats are often invoked to explain the maintenance of microbial diversity in the presence of competitive exclusion. Here we show that soil and plant-associated microbiota, cultivated ex situ in minimal synthetic environments with a single supplied source of carbon, universally re-assemble into large and dynamically stable communities with strikingly predictable coarse-grained taxonomic and functional compositions. We find that generic, non-specific metabolic cross-feeding leads to the assembly of dense facilitation networks that enable the coexistence of multiple competitors for the supplied carbon source. The inclusion of universal and non-specific cross-feeding in ecological consumer-resource models is sufficient to explain our observations, and predicts a simple determinism in community structure, a property reflected in our experiments.

ecology↗

bioRxiv2017

Intracellular metabolic circuits shape inter-species microbial interactions

Metabolite exchanges in microbial communities give rise to ecological interaction networks that influence ecosystem diversity and stability1-6. These exchanges depend on complex intracellular pathways thus raising the question of whether ecological interactions are inferable from genomes. We address these questions by integrating genome-scale models of metabolism7, to compute the fitness of interacting microbes, with evolutionary game theory, which uses these fitness values to infer evolutionarily stable interactions in multi-species microbial \"games\". After validating our approach using data on sucrose hydrolysis by S. cerevisiae, we performed over 80,000 in silico experiments to evaluate the rise of unidirectional and cross-feeding metabolic dependencies in populations of Escherichia coli secreting 189 amino acid pairs. We found that, despite the diversity of exchanged amino acids, most pairs conform to general patterns of inter-species interactions. However, several amino acid pairs deviate from these patterns due to pleiotropy and epistasis in metabolic pathways. To better understand the emergence of cross-feeding, we performed in silico invasion experiments and found possible evolutionary paths that could lead to such association. Overall, our study provides mechanistic insights into the rise of evolutionarily stable interdependencies, with important implications for biomedicine and microbiome engineering 8-10.

systems biology↗