New method ramps up protein production by a thousandfold

Researchers have discovered a method to supercharge protein production up to a thousandfold, an advance that may drive down costs of protein-based drugs, vaccines, and diagnostics.

Proteins are made of long chains of building block molecules called amino acids, and the process of producing them for medical or commercial applications can be complex, expensive, and time-consuming. Protein-based medicines such as insulin are synthesised by turning engineered bacteria into tiny protein-making factories, the scientists, including Indian-origin researcher Manasvi Verma from Washington University in the US, said.

Earlier research had found that the first few amino acids in a protein's chain had an important role in its production. In their current study, published in the journal Nature Communications, the researchers changed the sequence of the first few amino acids, and found that it increased protein production in the cells. "If you can make each bacterium produce 10 times as much protein, you only need one-tenth the volume of bacteria to get the job done, which would cut costs tremendously.

This technique works with all kinds of proteins because it's a basic feature of the universal protein-synthesising machinery," explained study senior author, Sergej Djuranovic from Washington University. As part of the study, the researchers made multiple variants of the genetic code behind the first few amino acids of the green fluorescent protein (GFP). The study noted that the GFP is a tool used in biomedical experiments to estimate the amount of protein in a sample by measuring the amount of fluorescent light produced. The researchers then inserted the different gene variants in the bacterium E.coli, generating 9,261 distinct versions of GFP -- all identical except for the very beginning.

According to the researchers, the different versions of GFP varied a thousand times from the dimmest to the brightest, indicating a thousandfold difference in the amount of protein produced. Certain combinations of amino acids at the third, fourth and fifth positions in the protein chain gave rise to sky-high amounts of protein, the scientists noted. They added that the same amino-acid triplets not only ramped up production of GFP -- which originally comes from jellyfish -- but also production of proteins from distantly related species like coral and humans.

"There are so many ways we could benefit from ramping up protein production," Djuranovic said. "In the biomedical space, there are many proteins used in drugs, vaccines, diagnostics, and biomaterials for medical devices that might become less expensive if we could improve production. Optimizing protein production could have a broad range of commercial benefits," he added.