Submitted to: Zeitschrift Fur Naturforschung
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/22/2002
Publication Date: 8/1/2002
Citation: Interpretive Summary: A natural herbicide was isolated from a strain of the plant pathogen Fusarium solani and its mode of action was studied. It was found that this compound is bioactivated when plant enzymes add phosphate groups to it. This activated sugar analog then inhibits the enzyme fructose-1,6-bisphosphate aldolase, a key enzyme in the breakdown of sugar during glycolysis.
Technical Abstract: F. solani NRRL 18883, devoid of the major toxins, produced large amounts of 2,5-anhydro-D-glucitol (AhG) that affected the growth of plants (I50 of 1.6 x 10-3 M). While AhG has no in vitro inhibitory activity, it was found to undergo enzymatic phosphorylation by the enzymes hexokinase and phosphofructokinase, yielding AhG-1,6- bisphosphate (AhG-BP), which in turn inhibited fructose-1,6- bisphosphate (FBP) aldolase. AhG-BP had an I50 value of 5.7 x 10-4 M on aldolase activity, and it competed with FBP for the catalytic site on the enzyme, with a Ki value of 1.0 x 10-4 M. The anomeric hydroxyl group on carbon 2 of FBP is required for the formation of an essential covalent bond (via protonated Schiff base) to amino functionality of lysine 225. The absence of this hydroxyl group on AhG-BP prevents the normal catalytic function of aldolase. Molecular modeling of the binding of AhG-BP to the catalytic pocket of plant aldolase shows that other atoms of the inhibitor can interact with the amino acids of the binding pocket in a manner similar to those of the substrate FBP. The ability of F. solani to produce a simple sugar analog that is bioactivated by the host plants in order to inhibit a major metabolic pathway further demonstrates the ability of a pathogen to utilized its host biochemical machinery to advantageous ends.