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

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.