Bioactivation of the fungal phytotoxin 2,5-anhydro-D-glucitol by glycolytic enzymes is an essential component of its mechanism of action.

An isolate of Fusarium solani, NRRL 18883, produces the natural phytotoxin 2,5-anhydro-D-glucitol (AhG). This fungal metabolite inhibited the growth of roots (150 of 1.6 mM), but it did not have any in vitro inhibitory activity. The mechanism of action of AhG requires enzymatic phosphorylation by plant glycolytic kinases to yield AhG-1,6-bisphosphate (AhG-1,6-bisP), an inhibitor of Fru-1,6-bisP aldolase. AhG-1,6-bisP had an I50 value of 570 microM on aldolase activity, and it competed with Fru-1,6-bisP for the catalytic site on the enzyme, with a Ki value of 103 microm. The hydroxyl group on the anomeric carbon of Fru-1,6-bisP is required for the formation of an essential covalent bond to zeta amino functionality of lysine 225. The absence of this hydroxyl group on AhG-1,6-bisP prevents the normal catalytic function of aldolase. Nonetheless, modeling of the binding of AhG-1,6-bisP to the catalytic pocket shows that the inhibitor interacts with the amino acid residues of the binding site in a manner similar to that of Fru-1,6-bisP. The ability of F. solani to produce a fructose analog that is bioactivated by enzymes of the host plant in order to inhibit a major metabolic pathway illustrates the intricate biochemical processes involved in plant-pathogen interactions.