Chemical insights into flexizyme-mediated tRNA acylation

A critical step in repurposing the cellular translation machinery for the synthesis of polymeric products is the acylation of transfer RNA (tRNA) with unnatural monomers. Toward this goal, flexizymes, ribozymes capable of aminoacylation, have emerged as a uniquely adept tool for charging tRNA with ever increasingly 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 flex-izymes 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 unprec-edented 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.

Automated summary

In this review, a library of monomer substrates tested for tRNA acylation with the flexizyme system is presented. Insights are provided for understanding the chemical factors influencing flexizyme-mediated tRNA acylation from a macroscopic perspective. It is concluded that flexizymes are primitive esterification catalysts with modest binding affinity to the monomer's aromatic recognition element. These robust and flexible flexizyme systems offer researchers unprecedented access to 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.