Boundary conditions for early 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 (1-6). 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 (9, 10) with physicochemical 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 acceptors can support the continuous production of a minimal ancient \"biomass\" composed of putative early biopolymers and fatty acids.