@article {Jinich245811,
	author = {Jinich, Adrian and Sanchez-Lengeling, Benjamin and Ren, Haniu and Goldford, Joshua E. and Noor, Elad and Sanders, Jacob N. and Segr{\`e}, Daniel and Aspuru-Guzik, Al{\'a}n},
	title = {A thermodynamic atlas of carbon redox chemical space},
	elocation-id = {245811},
	year = {2019},
	doi = {10.1101/245811},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {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.},
	URL = {https://www.biorxiv.org/content/early/2019/05/20/245811},
	eprint = {https://www.biorxiv.org/content/early/2019/05/20/245811.full.pdf},
	journal = {bioRxiv}
}