In Vitro Selection of Nucleic Acid Enzymes

Abstract

Among the enormous quantity and diversity of enzymes found in nature, researchers have confirmed the existence of only seven distinct classes of biological catalysts that are made of RNA rather than protein. As currently understood, the natural functions of these ribozymes are limited to phosphoester transfer and phosphoester hydrolysis reactions that occur with RNA or DNA substrates (Kruger et al. 1982; Guerrier-Takadaet al. 1983; Peebles et al. 1986; Paddy et al. 1986; Buzayan et al. 1986; Sharmeen et al. 1988; Saville and Collins 1990; Zimmerly et al. 1995). Although ribozymes are exceedingly rare and their biochemical functions are limited, they serve as essential components of the metabolic machinery of all living systems. It has been proposed that nucleic acids preceded proteins in the evolutionary history of biocatalysis, and that these primitive ribozymes catalyzed many of the reactions performed by modern protein enzymes (Gilbert 1986; Benner et al. 1989; Hirao and Ellington 1995). Over the course of 4 billion years of evolution, it appears that nature has determined that proteins are a superior format for constructing enzymes; however, the true capacity of nucleic acids for catalytic function remains to be fully defined.