Researchers have demonstrated that an artificial enzyme can function as a catalyst inside of a living cell triggering the expression of a desired protein. The study findings, published in Nature Communications, show that specially designed enzymes could be useful tools for performing biochemical functions in a live mammalian cell without causing harm to the cell.
Enzymes are natural catalysts of biochemical reactions but artificial catalysts have been shown to be more versatile in promoting different types of chemical synthesis processes. However, strictly controlled conditions are required within a cell for an artificial catalyst to function and those conditions are difficult to achieve in living cells.
Researchers in this most recent study overcame these restrictions by designing a metalloenzyme catalyst that turns on a gene switch. The switch then triggers a cascade of events ultimately ending in expression of a fluorescent protein. The metalloenzyme is the first to be engineered with a cell-penetrating moiety which enabled it to enter the cell. The enzyme also incorporated ruthenium as the catalytically active metal component. Once the metalloenzyme entered the HEK cell, it accelerated the release of a thyroid hormone. The hormone activated a gene switch which in turn led to the production of luciferase, a fluorescent reporter protein.
The proof-of-concept study demonstrates that an intracellular synthetic reaction enabled by a metalloenzyme is able to penetrate a live cell and perform a cell function. It opens the door for future artificial catalysts that can modify cellular functions or potentially produce a drug inside of a cell.
Image: An artificial metalloenzyme (blue) penetrates a mammalian cell, where it accelerates the release of a hormone (blue to red spheres). This activates a gene switch (circles with arrowheads), which then leads to the production of a fluorescent indicator protein (light green glow around the cell). Image courtesy of University of Basel, Yasunori Okamoto.