Programmable Biosensing with Plant Hormone Receptors
The ability to design biosensors that detect user-defined molecules has the potential to accelerate advances across biotechnology, from basic discovery to commercial applications in strain design, environmental monitoring, and healthcare diagnostics. We have developed a versatile sensing platform based on the plant receptor PYR1, a protein with a flexible binding pocket that naturally responds to the plant hormone abscisic acid (ABA). By introducing mutations to PYR1’s binding pocket and coupling PYR1 to its co-receptor HAB1, we created customizable “sense-and-respond” modules that can be reprogrammed to recognize new compounds. Using this system, we have generated hundreds of sensors with nanomolar to micromolar sensitivity for diverse targets, including substances of abuse, banned pesticides, FDA-approved drugs, environmental contaminants, and valuable industrial metabolites. To expand the platform, we redesigned the PYR1-HAB1 interface to create an orthogonal sensor system that functions independently of the native pathway. This enables multi-input, multi-output circuits, allowing cells to sense and respond to multiple chemicals at once. We demonstrated these capabilities by engineering bacteria, yeast, and plants with ligand-controlled genetic circuits that regulate biosynthetic pathways and report on environmental contaminants. The new sensing technologies developed with this platform include plants that sense banned pesticides, lateral flow devices for PFAS ‘forever compounds’, engineered yeast that sense and overproduce valuable metabolites, and a range of sensors that can be deployed in bacteria for sensing chemistry in the environment. Taken together, this work establishes PYR1-based receptors as a broadly applicable scaffold for developing programmable biosensors. These modules enable dynamic gene regulation, high-throughput strain engineering, and new sensing modalities in both microbes and plants, providing powerful tools for the next generation of biotechnology.
Bio: Ian Wheeldon is a professor of chemical and environmental engineering, the Director of the University of California, Riverside’s Center for Industrial Biotechnology, and the co-Director of the ExFAB Biofoundry. He received his Ph.D. in chemical engineering from Columbia University in 2009 and completed two years of postdoctoral training at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering at Harvard University. Wheeldon received a Master of Applied Science from the Royal Military College of Canada (2003), and a Bachelor of Applied Science (1999) from Queen’s University, Canada. His research focuses on microbial and plant synthetic biology.