Isomerization of the phytohormone precursor 12-oxophytodienoic acid (OPDA) in the insect gut: a mechanistic and computational study.

12-Oxophytodienoic acid (OPDA) is isomerized in the gut of herbivorous insects to tetrahydrodicranenone B (iso-OPDA). The transformation is achieved by a glutathione S-transferase present in the gut epithelium. Experiments with 9-[(2)H]-iso-OPDA demonstrated the complete retention of the deuterium atom in the product 11-[(2)H]-OPDA consistent with an intramolecular 1,3-hydrogen shift. Homology modeling based on the x-ray structure of a glutathione S-transferase from Anopheles gambiae revealed that the co-factor glutathione does not covalently bind to the substrate but appears to be involved in the initial deprotonation and enolization of the OPDA. The transformation resembles that of a mammalian GST-catalyzed isomerization of Δ(5)-3-ketosteroids to Δ(4)-3-ketosteroids or the conversion of prostaglandin A(1) to the biologically inactive prostaglandin B(1).