The origin of life required the emergence of metabolism, an autocatalytic network of enzymatic reactions that synthesize amino acids, nucleotides and cofactors. At the origin of metabolism there were no enzymes—how did it start? Empirical studies addressing early metabolic evolution are lacking. Harnessing protein structures for metabolic enzymes, we identify intermediate states in primordial metabolic assembly. We show that enzymatic metabolism in the universal common ancestor was incomplete, undergoing final assembly independently in the lineages leading to Bacteria and Archaea. Native transition metals—Fe0, Co0, Ni0, Pd0—served as the catalytic forerunners of both enzymes and cofactors at metabolic origin while phosphite supplied energy, as it phosphorylates AMP to ADP and serine to phosphoserine using native metal catalysts in water. Phosphite and native metals occur in serpentinizing hydrothermal systems, identifying an energy-supplying, catalytic site of metabolic origin. Cofactors liberated nascent metabolism from native metal catalysts, engendering its autocatalytic state.
Mrnjavac et al. (2026) studied this question.