Development of specific inhibitors of CYP707A, a key enzyme in the catabolism of abscisic acid.

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.