Designing KumaMax

The KumaMax project got its start in 2011 as an undergraduate project at the University of Washington (UW) for the international Genetically Engineered Machine (iGEM) competition. The iGEM competition is the premiere student team competition in synthetic biology. For iGEM, undergraduate students design, build, and test new biological molecules or systems over the course of the summer, then travel to MIT in the fall to present their work and compete against teams from around the world. The 2011 UW iGEM undergraduate team dreamed of treating celiac disease with an oral therapeutic, using computational protein design software developed at UW.

Members of the UW iGEM team holding their regional award in 2011. Photo: iGEM and David Donovan Evans

The 2011 UW iGEM team was led by our CSO, Dr. Ingrid Swanson Pultz, and Dr. Justin Siegel, who at the time were doctoral candidates in the lab of Dr. Sam Miller and a postdoctoral fellow in the lab of Dr. David Baker, respectively. Dr. David Baker is a computational biologist, UW Professor of Biochemistry, and Director of the Institute for Protein Design. Dr. Baker and his colleagues designed the Rosetta Molecular Modeling Suite, software that can assist in de novo protein and design.

The 2011 UW iGEM team decided to utilize this cutting edge software to design an enzyme that could specifically break down gluten in the stomach before the gluten can cause damage in the intestine.

The team identified kumamolisin-As (KumaWT), from the acidophilic bacterium Alicyclobacillus sendaiensis, as a starting template for an enzyme that could maintain activity in acidic conditions of the stomach. To create improved versions of KumaWT, the UW iGEM team used Rosetta to design a novel protein that has ~100x more specificity and activity for digestion of gluten protein than the original enzyme.

They called this new enzyme KumaMax, the first recombinant candidate enzyme therapeutic for celiac disease. The 2011 UW iGEM team won the international grand championship that year for KumaMax — the first undergraduate team to achieve this honor.

After receiving her doctoral degree, Dr. Pultz continued to work on the KumaMax prototype as a postdoc in the Baker lab and later as a faculty member at the Institute for Protein Design with her research scientist Clancey Wolf. Dr. Pultz received several grants and assembled a team of consultants and contractors to support the KumaMax project. Through an iterative process of computational design and testing, Dr. Pultz and her team arrived at a KumaMax variant with high enzymatic activity in acidic stomach conditions and demonstrated feasibility of production for this enzyme. In November 2016, PvP Biologics exclusively in-licensed the KumaMax technology from the UW.

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