Enzyme catalysis using thiol switching!
Imagine a container of tomatoes arriving at the container terminal in Aarhus. The papers state that the tomatoes are from Spain, but in reality, we have no way of knowing if that is true.
That is, unless we take a sample and have it analyzed in a laboratory, where scientists use DNA markers to determine whether the tomato is Spanish, South American or Chinese. This is both time-consuming and expensive.
But thanks to a scientific breakthrough, we will be able to examine tomatoes a lot quicker and cheaper, using special light producing proteins and our phones camera. Not right now, but in the near future.
The results were recently published in the journal Nature Communications.
"We have figured out how to instruct the proteins to generate light when specific DNA sequences appear. This could be used, as in the example with the tomatoes, but could also be useful in the healthcare sector, agriculture, or the pharmaceutical industry to analyze samples easily and cheaply," the senior author explains.
"We believe that there are huge possibilities in this."
The authors did this via “thiol switching”, using thiolated oligonucleotides: a protein is inactivated by conjugation to an oligonucleotide via a disulfide linkage; hybridization of the thiolated complementary oligonucleotide ensues disulfide exchange, the liberation of the enzyme, and the activation of enzymatic catalysis. In doing so, the researchers couple the most specific recognition event (hybridization) to the most effective tool of signal amplification (catalysis).
In the laboratory, they engineer molecules and cells. In some instances the team designs new molecules and install these into mammalian cells to bring new functions into the cell. But they also strive to build synthetic cells from scratch, one chemical building block at the time.
"We will hardly create new life this way any time soon. This is not why we are doing it. We are doing it to better understand and control natural cells."
“Our primary goal is to control the activity of molecules in space and time, inside and outside of the cell. Specifically we focus on enzymes that can create ATP, which is the cell’s fuel, and polymerases, which the cell uses to build RNA and DNA.”
By doing this kind of research, the team gets a deeper understanding of how cellular mechanisms work. And it is through this research they learned how to engineer proteins that generate light when certain DNA sequences are present – as in the example with the tomatoes.
Like building LEGO without the instruction manual
Designing cells from scratch is exciting, because our imagination is the only limit, the author explains and compares it to building with LEGO, but without an instruction manual and even without a defined set of building blocks.
"The first step is to assemble the membrane that defines the interior of an artificial cell. In our work, like in natural cells, the membrane is built of lipids that assemble in a bilayer, the author explains and continues:
"Next, we design ways to transfer information across the membrane. Last but not least we assemble the tools to interpret this information, which is done by putting together the parts inside the cell, including DNA and proteins.”
The research group strives to build intelligent synthetic cells, which are programmed to react in specific ways to the environment.
https://www.nature.com/articles/s41467-025-64636-z
https://sciencemission.com/Activation-of-enzymatic-catalysis
