As reported in the journal Nature, a team based at the Institute for Protein Design (IPD) at UW Medicine devised machine-learning algorithms that can create light-emitting enzymes called luciferases. Laboratory testing confirmed that the new enzymes can catalyze specific chemicals and emit light very efficiently. For the first time, scientists used machine learning to create brand-new enzymes, an important step in the field of de novo protein design, as new enzymes could have many uses across medicine and industrial manufacturing.

To create new luciferase enzymes, the team first selected chemicals called luciferins that they wanted the proteins to act upon. They then used software to generate thousands of possible protein structures that might react with those chemicals. The luciferase technology (LuxSit) developed by the Institute of Protein Design (IPD) at the University of Washington School of Medicine, researchers and licensed by Monod Bio, a Seattle based biotech company that uses state-of-the-art computational protein design to develop a new class of modular biosensors that emit a bioluminescent signal when the sensor recognizes its target.

Biosensors are molecular tools that detect the presence of specific molecules, even at very low concentrations. Monod’s biosensors are built from de novo engineered proteins developed in part using software from the (IPD). Combining these biosensors with the de novo luciferases will create new commercial opportunities for Monod Bio.

“I am thrilled that Monod Bio will be advancing LuxSit for its use in life sciences. This is just the first example of what we can now achieve using de novo proteins for biosensors and diagnostics,” said senior author David Baker, Ph.D., the Henrietta and Aubrey Davis Endowed Professor of Biochemistry at the University of Washington School of Medicine, a Howard Hughes Medical Institute investigator, Co-Founder of Monod Bio, and the Founder and Director of IPD.

“We were able to design very efficient enzymes from scratch on the computer, as opposed to relying on enzymes found in nature. This breakthrough means that custom enzymes for almost any chemical reaction could, in principle, be designed,” said Andy Yeh, Ph.D., Scientific Co-Founder at Monod Bio and first author on the paper.

“LuxSit and its underlying de novo protein design technology are fundamental to what we are developing at Monod Bio. With our expertise and resources we are uniquely positioned to fully unlock its potential to develop new biosensors and many other industry applications,” said Daniel-Adriano Silva, Ph.D., CEO & Co-Founder, Monod Bio. “We continue using LuxSit, machine learning, and de novo protein design to advance our unique biosensor pipeline aimed to improve human health. We look forward to announcing further details on our progress with the LuxSit platform later this year.”

About Monod Bio

Monod Bio is a pioneering company in the design of de novo protein-based biosensors that emit light when they recognize an intended target. The Company’s innovative biosensor platform technology uses computational de novo protein design to create highly modular biosensing nanoswitches that enable rapid, sensitive, and cost-effective analytical assays. The company is founded on technology developed in David Baker’s group at the University of Washington’s Institute for Protein Design, including the LucCage biosensor platform and the LuxSit de novo luciferase technology. Monod Bio’s proprietary technology has been published in several peer-reviewed journals, including Nature and Nature Biotechnology, expanding our understanding of what is possible with de novo protein biosensors. Monod Bio is based in Seattle, WA. For additional information, visit www.monodbio.com.

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