Frontiers in Genomics: Sean Cutler
Programming new plant functions using engineered signaling modules

Resumen

Plants sense the hormone abscisic acid (ABA) using chemical-induced dimerization (CID) modules, including the receptor PYR1 and HAB1, a protein phosphatase inhibited by ligand-activated PYR1. This system is unique because of the relative ease with which ligand recognition can be reprogrammed. To expand the PYR1 system, we designed an orthogonal response module that harbors a dimer-interface salt bridge that prevents cross-activation of the wild-type module, as supported by X-ray crystallographic, biochemical, and in vivo analyses. We used this module to create new CID modules, PYR1*MANDI/HAB1* and PYR1*AZIN/HAB1*, that possess nM sensitivities to their activating ligands mandipropamid and azinphos-ethyl. Experiments in A. thaliana and S. cerevisiae demonstrate the sensitive detection of banned organophosphate contaminants using living biosensors and the construction of multi-input/output genetic circuits. Our new modules enable ligand-programmable multichannel CID systems for plant and eukaryotic synthetic biology that can empower new plant- and microbe-based sensing modalities. We also highlight engineered plant hormone sensors for creating inducible phenotypes in Arabidopsis, diverse Citrus varieties, and Setaria. Lastly, by developing a high throughput screening platform to conduct unbiased screens, we demonstrate that PYR1-derived sensors can recognize a substantial fraction of drug-like chemical space, which suggests that designing sensors for user-specified molecules and, thus, ligand-controlled plant traits is feasible. The biochemical features that make PYR1 an excellent scaffold for designing orthogonal receptor-ligand interactions are shared by GA and strigolactone receptors, which suggest that other plant hormone-sensing systems can be harnessed to reprogram hormonal and transcription responses so that ligands of choice control them.

Sean Cutler. Botany and Plant Science Department, University of California at Riverside US

https://profiles.ucr.edu/app/home/profile/cutler

Frontiers in Genomics