Scientists are using AlphaFold in their research to strengthen an enzyme that’s vital to photosynthesis, paving the way for more heat-tolerant crops.

As global warming accompanies more droughts and heatwaves, harvests of some staple crops are shrinking. But less visible is what is happening inside these plants, where high heat can break down the molecular machinery that keeps them alive.

At the heart of that machinery lies a sun-powered process that supports virtually all life on Earth: photosynthesis. Plants use photosynthesis to produce the glucose that fuels their growth via an intricate choreography of enzymes inside plant cells. As global temperatures rise, that choreography can falter.

Berkley Walker, an associate professor at Michigan State University, spends his days thinking about how to keep that choreography in step. "Nature already holds the blueprints for lots of enzymes that can handle heat," he says. "Our job is to learn from those examples and build that same resilience into the crops we depend on."

Walker’s lab focuses on a vital enzyme in photosynthesis called glycerate kinase (GLYK), an enzyme that helps plants recycle carbon during photosynthesis.One hypothesis is that, if it gets too hot, GLYK stops working, and photosynthesis fails.

Walker’s team set out to understand why. Because the structure of GLYK has never been determined experimentally, they turned to AlphaFold to predict its 3D shape, not only in plants but also in a heat-loving algae that thrives in volcanic hot springs. By taking AlphaFold’s predicted shapes and plugging them into sophisticated molecular simulations, the researchers could watch as these enzymes flexed and twisted as the temperature rose.

That’s when the problem came into focus: three flexible loops in the plant version of GLYK wobbled out of shape at high heat.

Experiments alone could never deliver such insights, says Walker: “AlphaFold enabled access to experimentally unavailable enzyme structures and helped us identify key sections for modification.”

Armed with this knowledge, the researchers in Walker’s lab made a series of hybrid enzymes that replaced the unstable loops in the plant GLYK with more rigid ones borrowed from the algae’s GLYK. One of these performed spectacularly, remaining stable at temperatures up to 65 °C.