Multilayered substructures of a non-enzymatic chemical reaction network for synthesizing sugars

In biological chemical reactions, substructures formed through multi-step enzymatic reactions organize into large chemical reaction networks (CRNs) that produce complex and sophisticated functions. Recently, significant attention has been paid to artificial, non-enzymatic control of multi-step chemical reactions aimed at synthesizing compounds with structural complexity. However, the synergistic effects arising from the activation of different substructures within a CRN by multiple catalysts remain unexplored. Here we focus on the formose reaction as a non-enzymatic CRN to demonstrate that the complementary activation of multiple substructures by distinct catalysts leads to the emergence of novel functions. Statistical analyses of temporal changes in compound concentrations during reactions catalyzed by γ-Al₂O₃ and phosphate buffer suggested the presence of a third catalytic species. The experimental results revealed synergistic effects among the substructures activated by γ-Al₂O₃, phosphates, and this third species. Our findings demonstrate that multiple catalysts can be designed to control the functions of CRNs.