Expanding the Scope of Ribosome‐Mediated Biosynthesis in vitro using tRNA‐Aminoacylating Ribozyme

Abstract

Proteins are synthesized within ribosomes through the polymerization of amino acids (AAs). This process requires prior activation of AAs through aminoacylation that attaches them to their corresponding transfer RNAs (tRNAs). Within cells, this attachment is facilitated by aminoacyl‐tRNA synthetase, resulting in a tRNA:AA conjugate. A set of ribozymes developed to acylate tRNA with non‐canonical substrates enables this process outside the confines of living cells, thereby facilitating the synthesis of novel bio‐based products. In modern biotechnology, aminoacylating ribozymes contribute to the production of innovative bio‐based materials bearing functional non‐canonical chemical substrates (NCSs) and fill the gaps in synthesizing unique polymeric backbones, extending the scope beyond traditional peptide bonds. This review summarizes current understanding of flexizymes at the molecular level and their application in generating exceptional polymeric backbones through ribosome‐mediated synthesis in vitro.

Triphasic Development of the Genetic Code

“…Moreover, the newer Fxs are capable of cooperating with the ribosome and bacterial elongation factor EF-P to build peptide bonds. They are therefore versatile adaptations of self-aaRSs useful for introducing ncAAs into peptides in cell-free systems through amino acid activation by non-ATP activators. − The elaboration of the Fxs from esterifying enzymes to ribosome-type systems for peptide synthesis confirms the plausibility of the self-aaRS origin of tRNA (Figure ) as the starting point of ribosomal translation and genetic code.…”