Recreating ancient metabolic pathways before enzymes

The biochemistry of all living organisms uses complex, enzyme-catalyzed metabolic reaction networks. Yet, at life’s origins, enzymes had not yet evolved. Therefore, it has been postulated that non-enzymatic metabolic pathways predated their enzymatic counterparts. In this account article, we describe our recent work to evaluate whether two ancient carbon fixation pathways, the rTCA (reductive tricarboxylic acid) cycle and the reductive AcCoA (Wood-Ljungdahl) pathway, could have operated without enzymes and therefore have originated as prebiotic chemistry. We also describe the discovery of an Fe²⁺-promoted complex reaction network that may represent a prebiotic predecessor to the TCA and glyoxylate cycles. The collective results support the idea that most central metabolic pathways could have roots in prebiotic chemistry.