Dynamic control of plant water use using designed ABA receptor agonists

Abstract

Drought causes crop losses worldwide, and its impact is expected to increase as the world warms. This has motivated the development of small-molecule tools for mitigating the effects of drought on agriculture. We show here that current leads are limited by poor bioactivity in wheat, a widely grown staple crop, and in tomato. To address this limitation, we combined virtual screening, x-ray crystallography, and structure-guided design to develop opabactin (OP), an abscisic acid (ABA) mimic with up to an approximately sevenfold increase in receptor affinity relative to ABA and up to 10-fold greater activity in vivo. Studies in Arabidopsis thaliana reveal a role of the type III receptor PYRABACTIN RESISTANCE-LIKE 2 for the antitranspirant efficacy of OP. Thus, virtual screening and structure-guided optimization yielded newly discovered agonists for manipulating crop abiotic stress tolerance and water use.

Recent Advances in Plant Chemical Biology of Jasmonates

“…However, there are few successful examples of 'biased' plant hormone receptor agonists. Cutler's group successfully developed the ABA receptor agonists [39] pyrabactin [40,41], quinabactin [42], cyanabactin [43], and opabactin [44], which were identified by random screening of a large-scale chemical library, and exhibited remarkable selectivity among 15 ABA receptor subtypes. The same method also resulted in the identification of SPL7, a femtomolar agonist selective for a strigolactone receptor ShHTL7 involved in the seed germination of parasitic plant Striga hermonthica [45].…”

Identification of Novel Inhibitors of a Plant Group A Protein Phosphatase Type 2C Using a Combined In Silico and Biochemical Approach

“…Much effort has been dedicated to the identification of synthetic compounds that mimic the effect of ABA. The most well-characterized are a tetrafluoro derivative of quinabactin (AMF4) pyrabactin, cyanabactin, and opabactin (Okamoto et al, 2013;Cao et al, 2017;Vaidya et al, 2017;Vaidya et al, 2019). Quinabactin is more efficient than pyrabactin in regulating the ABA response and is known to affect plant vegetative responses, especially adaptive responses that are essential for crop quality and quantity.…”

“…Quinabactin is more efficient than pyrabactin in regulating the ABA response and is known to affect plant vegetative responses, especially adaptive responses that are essential for crop quality and quantity. Cyanabactin treatment significantly affects stomatal conductance and regulates ABA gene expression (Vaidya et al, 2017), while opabactin is currently the most effective tool for manipulating efficiency of water use (Vaidya et al, 2019;Lozano-Juste et al, 2020). Mandipropamid is another example of a compound that has the ability to activate an engineered PYR1 receptor and has significant potential for the modulation of ABA signaling in crops (Park et al, 2015;Rodriguez and Lozano-Juste, 2015).…”

“…To date, the function of plant PP2Cs has been analyzed mainly by biochemical, molecular, and other biological methods due to lack of any specific PP2C inhibitors; if such inhibitors were available, they would be extremely useful tools in plant research, being complementary to other resources that can mimic the ABA response (Kim et al, 2011;Okamoto et al, 2013;Rodriguez and Lozano-Juste, 2015;Takeuchi et al, 2016;Cao et al, 2017;Vaidya et al, 2017;Vaidya et al, 2019). Virtual screening approaches for mammalian PP2C inhibitors have been undertaken, but with modest success.…”

Identifying Cancer-Relevant Mutations in the DLC START Domain using Evolutionary and Structure-Function Analyses

“…In plants, signaling of the hormone abscisic acid (ABA) is mediated by its minimal START domain receptor [44]. Opabactin, a rationally designed agonistic START ligand, has a 7-fold stronger affinity than the native ligand, and increases ABA signaling outputs in vivo by a factor of 10 [45].…”