Scientists rewire bacteria to build ‘designer’ proteins on demand

11 MARCH 2026

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.

Artificial amino acids

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.
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.

Discovery of the transporter and Protein-cutting enzyme

In the new study, the researchers pinned down the exact molecule ferrying the peptides into the cell.
In the absence of the transporter — the main bacterial system that normally imports small protein fragments as food — the cells almost completely lost the ability to use the artificial amino acids bound to the peptides.
That was a sign this specific molecule was the smuggler.
Once the peptides were inside, the cell’s own protein-cutting enzymes unpacked them.
The researchers were able to confirm this: when they removed the enzymes that normally cut peptides into individual amino acids, the cell’s protein production dropped.
Taken together, the transporter brought the cargo in, then ordinary enzymes freed the artificial amino acid so the cell’s ribosome could use it.

Significance:

The study makes it “possible to produce designer proteins containing unnatural amino acids just as efficiently as their natural counterparts”.
These could be genuinely multifunctional proteins, such as an antibody that carries a drug at one engineered position.