Development of Specific Inhibitors of CYP707A, a Key Enzyme in the Catabolism of Abscisic Acid

Abstract

Abscisic acid (ABA) is a plant hormone involved in stress tolerance, stomatal closure, seed dormancy, and other physiological events. Although ABA is registered as a farm chemical (plant growth regulator), its practical use has been limited, mainly due to its weak effect in field trials, which is considered to be due to its rapid inactivation through biodegradation. Catabolic inactivation of ABA is mainly controlled by ABA 8'-hydroxylase (CYP707A), which is the cytochrome P450 catalyzing the C8'-hydroxylation of ABA into 8'-hydroxy-ABA and its more stable tautomer, phaseic acid, which has much lower hormonal activity than ABA. Thus, a specific inhibitor of CYP707A is promising not only as a chemical probe for the mechanism of ABA action, but also because of its potential use in agriculture and horticulture. This review article focuses on our recent research on the development of two types of specific inhibitors of CYP707A: the ABA analogue-type inhibitors that were designed on the basis of differences between the structural requirements for CYP707A and for ABA activity, and the azole-type P450 inhibitors that were developed by conformational restriction or enlargement of the plant growth retardant uniconazole.

Abscisic Acid as Pathogen Effector and Immune Regulator

“…Similar approaches are currently also pursued in the plant sciences where antagonistic ABA analogs have been designed (Takeuchi et al, 2014), and pyrabactin variants are utilized as more stable and chemically unrelated ABA agonists (Overtveldt et al, 2015). An alternative treatment approach is to manipulate ABA homeostasis indirectly by targeting the different mechanisms that influence the levels of free intracellular ABA (Todoroki and Ueno, 2010). A conceptually similar approach has already been tried in animal systems by treatments with a herbicide (Fluridone), which is known to influence ABA levels in plants (Magnone et al, 2013).…”

Expression profiling of ABA pathway transcripts indicates crosstalk between abiotic and biotic stress responses in Arabidopsis

“…The expression levels of 5 genes involved in ABA biosynthesis [30][31][32], 4 genes involved in ABA catabolism [33,34], and 12 ABA-responsive genes were also checked in this study and some of them were used as positive controls. All AGI IDs were input into The Bio-Array Resource for Plant Biology (http://bar.utoronto.ca/) using the tool of "e-Northerns w. Expression Browser" [35].…”

Chemical biology of abscisic acid

“…These studies showed important ABA functional groups for ABA J Plant Res (2011) 124:549-557 553 activities (Todoroki and Ueno 2010). Recently, the crystal structures of intercellular ABA receptors were reported Hubbard et al 2010), thus the results of SAR studies can be largely explained by the crystal structures of ABA receptors.…”