Scientists rewire bacteria to build ‘designer’ proteins on demand Premium

Scientists have engineered bacteria to produce designer proteins by smuggling artificial amino acids, enabling precise drug delivery and multifunctional applications.

Researchers have found a way to hijack the natural protein-making facilities of bacteria to manufacture specific proteins of interest. They did this by turning a ‘nutrient gate’ on a bacterial cell into a Trojan horse that could ferry artificial amino acids into cells to make these proteins.

The study, conducted by teams at ETH Zurich in Switzerland and the Technical University of Munich in Germany, was published in Nature. 

All proteins are made of some combination of the 20 natural amino acids. In the lab, chemists can also synthesise thousands of artificial amino acids, many of which have completely new properties. For example, if an amino acid called p-azido-L-phenylalanine can be built into a protein, it would allow scientists to attach drugs to the protein at a precise spot, helping it treat some disease.

The challenge however has been to get cells’ protein-making machines to use these artificial amino acids.

In the 1980s, Peter Schultz and his colleagues at the University of California, Berkeley, laid the foundations of incorporating artificial amino acids into proteins at specific sites. Over the years, scientists have expanded this toolkit to incorporate artificial amino acids in proteins that cells make. 

Yet one problem has persisted: the struggle to get enough artificial amino acids into the cell. Most lab-made amino acids struggle to cross the cell membrane and enter the cytoplasm, where the ribosomes synthesise proteins. This is because the side chains on artificial amino acids are very water-loving whereas the core of the cell-membrane is water-repelling.