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

In biological chemical reactions, such as those found in metabolism, 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. Sequential reactions, where multiple catalysts each drive specific steps, have emerged as a promising strategy to enhance overall efficiency; however, the synergistic effects arising from the activation of different substructures within a CRN by multiple catalysts, and the emergent functions resulting from the combination of these substructures, remain largely unexplored. In this study, 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. We conducted a statistical analysis of temporal changes in compound concentrations during reactions catalyzed by γ-Al ₂ O ₃ and a phosphate buffer solution. The results suggested the presence of a third catalytic species and revealed synergistic effects among the substructures activated by γ-Al ₂ O ₃ , phosphates, and this third species. Our findings demonstrate that the synergistic effects of multiple catalysts can be harnessed to design and control the functions of CRNs.