Substrate-directed formation of small biocatalysts under prebiotic conditions.

One of the most debated issues concerning the origin of life, is how enzymes which are essential for existence of any living organism, evolved. It is clear that, regardless of the exact mechanism, the process should have been specific and reproducible, involving interactions between different molecules. We propose that substrate templating played a crucial role in maintaining reproducible and specific formation of prebiotic catalysts. This work demonstrates experimentally, for the first time, substrate-directed formation of an oligopeptide that possesses a specific catalytic activity toward the substrate on which it was formed. In our experiments we used the substrate O-nitrophenol-beta-D-galactopyranoside (ONPG) as a molecular template for the synthesis of a specific catalyst that is capable of cleaving the same substrate. This was achieved by incubation of the substrate with free amino acids and a condensing agent (dicyandiamide) at elevated temperatures. A linear increase with time of the reaction rate (d[product]/d2t), pointed to an acceleration regime, where the substrate generates the formation of the catalyst. The purified catalyst, produced by a substrate-directed mechanism, was analyzed, and identified as Cys2-Fe+2. The mechanism of substrate-directed formation of prebiotic catalysts provides a solution to both the specificity and the reproducibility requirements from any prebiotic system which should evolve into the biological world.