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.