RNA-catalyzed CoA, NAD, and FAD synthesis from phosphopantetheine, NMN, and FMN

A novel in vitro selection method was developed to isolate RNA sequences wi th coenzyme-synthesizing activities. We used size-heterogeneous libraries c ontaining randomized ribonucleotide sequences of four different lengths (30 N, 60N, 100N, and 140N), all with 5'-ATP initiation. Two RNAs, CoES7 (30N) and CoES21 (60N), are able to catalyze the synthesis of three common coenzy mes, CoA, NAD, and FAD, from their precursors, 4'-phosphopantetheine, NMN, and FMN, respectively. Both ribozymes require divalent manganese for activi ties. The results support the availability of these coenzymes in an RNA wor ld, and point to a. chemical explanation for the complex bipartite structur es of many coenzymes.