Studies on creation of specific regulators for abscisic acid catabolism and signal transduction

Abstract

Abscisic acid （ABA） has critical roles in many physiological processes including seed dormancy, stomatal closure and adaptive responses to abiotic stress.　Synthetic positive or negative regulators of ABA function are expected to use as not only chemical tools for research in plant biology but also plant growth regulators for agriculture application.　We developed inhibitors of ABA-inactivating enzymes as the positive regulators and antagonists of ABA receptors as the negative regulators.　（1） Specific inhibitors of ABA-inactivating enzymes: Key enzymes for ABA inactivation are ABA 8′-hydroxylases, cytochrome P450 enzymes classified into the CYP707A subfamily.　Because the tertiary structure of CYP707A has never been clarified, we developed the CYP707A inhibitors as ABA analogs （AHI） or azoles （abscinazoles） by lead optimization based on structure-activity relationship.　These inhibitors conferred drought tolerance in plants.　（2） Antagonists of ABA receptors: ABA signaling is repressed by PP2Cs, but stress-induced ABA binds PYL, which then bind and inhibit PP2Cs.　X-ray structures of several receptor-ABA complexes revealed a tunnel above ABA’s 3′-CH and 4′-CO that opens at the PP2C binding interface.　Because ABA analogs with sufficiently long 3′ or 4′ chains were predicted to traverse this tunnel and block PYL-PP2C interactions, we designed and synthesized AS6 and PAN.　These compounds functioned as a potent ABA antagonist to block multiple stress-induced ABA responses in vivo.