(115b) Enabling Biosynthesis of Complex Proteins in Bacteria Via Ribosome Reprogramming
AIChE Annual Meeting
2006
2006 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Advances in Protein Expression and Post-Translational Modification
Monday, November 13, 2006 - 3:35pm to 3:55pm
In addition to carrying out protein translation, emerging evidence indicates that ribosomes play an active and important role in the post-translational processing (e.g., on-pathway folding, membrane transport) of nascent protein chains. Although these non-synthetic capabilities are still obscure, most have been linked to the polypeptide exit tunnel, a region through which all newly-made proteins travel following their synthesis at the site of peptide bond catalysis (where the tunnel begins). We are developing a mechanistic understanding of the ribosomal exit tunnel's many functional roles and using this information to create novel technologies for the expression, engineering and folding of complex proteins in bacteria. In particular, we will demonstrate how this approach has enabled enhanced production of multidomain eukaryotic proteins in prokaryotic systems, a problem which represents a major bottleneck to the biotechnology enterprise. Finally, we will discuss how these technologies might spawn the engineering of entirely new functionalities to the ribosome by means of genetic manipulations.