The quantitative metabolome is shaped by abiotic constraints

Abstract

Living systems formed and evolved under governing constraints that characterize their interactions with the inorganic world. These interactions are definable using basic physico-chemical principles. Here, we formulate a comprehensive set of ten governing abiotic constraints that define possible quantitative metabolomes. We apply these constraints to a metabolic network of Escherichia coli that represents 90% of its metabolome. We show that the quantitative metabolomes allowed by the abiotic constraints are consistent with metabolomic and isotope labeling data. We find that: (i) Network-wide characterization of charge-, proton- and magnesium-related constraints shape transcriptional regulatory responses to osmotic stress; (ii) Proton and charge imbalance underlie transcriptional regulatory responses to acid stress; (iii) Abiotic constraints drive the evolution of transport systems, such as high-affinity phosphate transporters. Thus, quantifying the constraints that the inorganic world imposes on living systems provides insights into their key characteristics, helps understand the outcomes of evolutionary adaptation, and should be considered as a fundamental part of theoretical biology and for understanding the constraints on evolution.