Chemical Plants at the Cellular Scale

“If you can’t find what you want in nature, you can use engineering to do better than nature has done,” says Kristala Jones Prather ’94, associate professor of chemical engineering.

The Prather Lab manipulates microbes, such as E. coli, to produce chemical compounds utilized in pharmaceutical products, building materials, or biofuels—increasing yield or eliminating the need to add chemical inducers to control the production process. For instance, a February 2017 paper in Nature Biotechnology demonstrated a genetic switch that could optimize production of glucaric acid, a chemical with uses ranging from therapeutic treatments of high cholesterol and cancer to improving polymers like nylon and polyester.

That proof of concept, says Prather, is transferrable into bacteria or yeast generating other useful chemicals.

Prather’s research takes two directions—first, “We’re focused on coming up with new ways to identify where in nature to go to find these enzymes,” she says. “We need good ways to sort through the possibilities.”

Then, the researchers alter cell behavior so that as much as possible of the desired product is produced. “We have to get cells to use the sugars that they would usually use for growth for something else. We’re competing with the inherent propensity of a cell to make more of itself. That tension is something you always have to deal with in metabolic engineering. We need them to not be so selfish and not take that feedstock.”

As for how they do that, Prather uses the analogy of a chemical plant: material is moved from one place to another via valves that can be switched on and off. Cells can achieve this through quorum sensing, a phenomenon in which inducer concentration builds up and triggers the genes that affect the production of the target chemicals. “We have a library of strains where the timing of that switch varies,” describes Prather. “We work out the best time to close off the valves. We’re pulling pieces that naturally exist in biology and adapting them for our own purposes.”