Genetic code expansion (GCE) is a powerful method to incorporate artificial amino acids into polypeptide chains to create synthetic proteins with novel functions, with many applications ranging from discovery science to molecular medicine. Until recently, this method has been mostly confined to small individual proteins representing a limited repertoire of cellular activity. Biological function in humans, however, is typically catalyzed by large protein machines, often comprising ten or more individual protein subunits. An international team of scientists from University of Bristol, EMBL and the Karlsruhe Institute of Technology developed MultiBacTAG™, a powerful system to enable genetic code expansion in complex multiprotein machines.
Scientists can now conveniently produce recombinant eukaryotic proteins with synthetic amino-acids inserted at specific locations, thanks to the MultiBacTAG™. MultiBacTAG’s applications include glycoengineering proteins compatible with human tissue studies, fluorescence labelling of specific targets to measure structure and dynamics in proteins, and amino acid cross-linking in order to map protein binding interfaces.
The platform can provide insight into how specific protein complexes function, as well as possibilities to custom-design proteins for therapeutic biotechnology and pharmaceutical applications. In their paper, for example, the team used MultiBacTAG to engineer Herceptin – an antibody that associates with cancer cells – to recognize breast cancer cells in human tissue.