Thermodynamic dissipation constrains metabolic versatility of unicellular growth

From deep hydrothermal vents to artificial laboratory conditions, unicellular organisms grow in almost any environment. This is due to metabolic versatility, the capacity of metabolism to extract energy and matter from vastly different chemical substrates. Since growth occurs far from thermodynamic equilibrium, the second law of thermodynamics, which establishes the unavoidability of energy dissipation, has long been believed to pose key constraints to life. Yet, such constraints remain largely unknown. Here, we integrate published data spanning eight decades of experiments on unicellular chemotrophic growth and compute the corresponding thermodynamic dissipation. Due to its wide span in chemical substrates and microbial species, this dataset samples the versatility of metabolism. We find two empirical thermodynamic rules that constrain metabolic versatility and thus unicellular growth. First, the amount of energy dissipation per unit of biomass grown is largely conserved across metabolic types and domains of life. Second, aerobic respiration exhibits a trade-off between dissipation and growth, which reflects in its high thermodynamic efficiency. Using tools from non-equilibrium thermodynamics, we identify the origin of these rules in the forces that drive and oppose growth. Our results show that dissipation imposes tight constrains to metabolic versatility far from equilibrium. They further suggest that evolutionary pressure on the thermodynamic features of metabolism may have driven the origin and persistence of aerobic respiration. Overall, this work establishes the central role of non-equilibrium thermodynamics in unicellular life.