Chemical insights into flexizyme-mediated tRNA acylation

Abstract

A critical step in repurposing the cellular translation machinery for the synthesis of polymeric products istheacylation of transfer RNA (tRNA) with unnatural monomers. Toward this goal, flexizymes, ribozymescapable of aminoacylation, have emerged as a uniquely adept tool for charging tRNA with everincreasingly diverse substrates. In this review, we present a library of monomer substrates that have been tested for tRNA acylation with the flexizyme system. From this mile-high view, we provide insights for understanding the chemical factors that influence flexizyme-mediated tRNA acylation. We conclude that flexizymes are primitive esterification catalysts that display a modest binding affinity to the monomer's aromatic recognition element. Together, these robust, yet flexible, flexizyme systems provide researchers with unprecedented access for preparing unnatural acyl-tRNA and the opportunity to repurpose the translation machinery for the synthesis of novel biologically derived structures beyond native proteins and peptides.