SUBSTRATE-DIRECTED FORMATION OF SMALL BIOCATALYSTS UNDER PREBIOTIC CONDITIONS

One of the most debated issues concerning the origin of life, is how e nzymes which are essential for existence of any living organism, evolv ed. It is clear that, regardless of the exact mechanism, the process s hould have been specific and reproducible, involving interactions betw een different molecules. We propose that substrate templating played a crucial role in maintaining reproducible and specific formation of pr ebiotic catalysts. This work demonstrates experimentally, for the firs t time, substrate-directed formation of an oligopeptide that possesses a specific catalytic activity toward the substrate on which it was fo rmed. In our experiments we used the substrate o-nitrophenol-beta-D-ga lactopyranoside (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]/d(2)t), pointed t o an acceleration regime, where the substrate generates the formation of the catalyst. The purified catalyst, produced by a substrate-direct ed mechanism, was analyzed, and identified as Cys(2)-Fe+2. The mechani sm of substrate-directed formation of prebiotic catalysts provides a s olution to both the specificity and the reproducibility requirements f rom any prebiotic system which should evolve into the biological world .