AlphaFold Helps Build a Heat-Proof Enzyme for Photosynthesis

A hybrid plant enzyme engineered with the help of AlphaFold stayed stable at temperatures up to 65 °C, according to Berkley Walker's lab at Michigan State University. The result points to a practical route toward crops that can survive the heatwaves and droughts that are already shrinking harvests of staple foods.

The target is an enzyme called glycerate kinase, or GLYK, which helps plants recycle carbon during photosynthesis. The lab's working hypothesis is simple: when it gets too hot, GLYK stops working, and photosynthesis fails. High heat does not just wilt leaves. It breaks down the molecular machinery inside plant cells, and the intricate choreography of enzymes that converts sunlight into glucose falters as global temperatures rise.

Walker, an associate professor at Michigan State University, frames the problem as one of borrowing from nature. "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."

There was a catch. No one had ever determined the structure of GLYK experimentally. So Walker's team 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. The researchers then fed those predicted shapes into molecular simulations and watched how the enzymes flexed and twisted as the temperature climbed.

The simulations exposed the failure point. Three flexible loops in the plant version of GLYK wobbled out of shape at high heat. That level of insight was out of reach for conventional experiments, according to Walker. "AlphaFold enabled access to experimentally unavailable enzyme structures and helped us identify key sections for modification," he says.

With those sections identified, the lab built a series of hybrid enzymes. The researchers replaced the unstable loops in plant GLYK with more rigid ones borrowed from the algae's version of the enzyme. One of the hybrids performed spectacularly, remaining stable at temperatures up to 65 °C.

The next step moves from the bench to the field. Walker plans to grow plants engineered to produce these hybrid enzymes and test whether they can hold their own when the heat is on. If the approach works, it could extend to other temperature-sensitive enzymes across photosynthesis, reinforcing the core process that underpins plant growth.

The stakes are straightforward. Heatwaves and droughts driven by global warming are already cutting into harvests, and photosynthesis supports virtually all life on Earth. A method for stabilizing the enzymes at the center of that process could become a molecular toolkit for adapting a range of crops to a warming world — and for protecting food production over the coming decades.

The work also shows how protein-structure prediction is functioning as working laboratory infrastructure rather than a novelty. In this case, AlphaFold delivered structural access that crystallography had not, and the simulation pipeline converted that access into a specific engineering target. Walker's team now has to prove the enzymes perform inside living plants, and that heat-stable photosynthesis translates into heat-stable yields.