ADENOSINE-5'-PHOSPHATE DEAMINASE A NOVEL HERBICIDE TARGET

The isolation of carbocyclic coformycin as the herbicidally active com ponent from a fermentation of Saccharothrix species was described prev iously (B.D. Bush, G.V. Fitchett, D.A. Gates, D. Langley [1993] Phytoc hemistry 32: 737-739). Here we report that the primary mode of action of carbocyclic coformycin has been identified as inhibition of the enz yme AMP deaminase (EC 3.5.4.6) following phosphorylation at the 5' hyd roxyl on the carbocyclic ring in vivo. When pea (Pisum sativum L. var Onward) seedlings are treated with carbocyclic coformycin, there is a very rapid and dramatic increase in ATP levels, indicating a perturbat ion in purine metabolism. Investigation of the enzymes of purine metab olism showed a decrease in the extractable activity of AMP deaminase t hat correlates with a strong, noncovalent association of the phosphory lated natural product with the protein. The 5'-phosphate analog of the carbocyclic coformycin was synthesized and shown to be a potent, tigh t binding inhibitor of AMP deaminase isolated from pea seedlings. Thro ugh the use of a synthetic radiolabeled marker, rapid conversion of ca rbocyclic coformycin to the 5'-phosphate analog could be demonstrated in vivo. It is proposed that inhibition of AMP deaminase leads to the death of the plant through perturbation of the intracellular ATP pool.