Environmental boundary conditions for the origin of life converge to an organo-sulfur metabolism

It has been suggested that a deep memory of early life is hidden in the architecture of metabolic networks, whose reactions could have been catalyzed by small molecules or minerals prior to genetically encoded enzymes. A major challenge in unraveling these early steps is assessing the plausibility of a connected, thermodynamically consistent proto-metabolism under different geochemical conditions, which are still surrounded by high uncertainty. Here we combine network-based algorithms with physico-chemical constraints on chemical reaction networks to systematically show how different combinations of parameters (temperature, pH, redox potential and availability of molecular precursors) could have affected the evolution of a proto-metabolism. Our analysis of possible trajectories indicates that a subset of boundary conditions converges to an organo-sulfur-based proto-metabolic network fueled by a thioester- and redox-driven variant of the reductive TCA cycle, capable of producing lipids and keto acids. Surprisingly, environmental sources of fixed nitrogen and low-potential electron donors seem not to be necessary for the earliest phases of biochemical evolution. We use one of these networks to build a steady-state dynamical metabolic model of a proto-cell, and find that different combinations of carbon sources and electron donors can support the continuous production of a minimal ancient “biomass” composed of putative early biopolymers and fatty acids.