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United States Department of Agriculture

Agricultural Research Service

Title: Physiological Factors Influencing the Antifungal Activity of Zopfiellin

Authors
item Futagawa, Mistugu - NISSAN CHEMICAL IND.JAPAN
item Wedge, David
item Dayan, Franck

Submitted to: Pesticide Biochemistry and Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 1, 2002
Publication Date: August 1, 2002

Interpretive Summary: Zopfiellin is a natural product produced by a fungus called Zopfiella curvata. This compound has antifungal activity and its mode of action was investigated. We found that the activity of zopfiellin was affected by pH, probably as a result of a change in the structure that prevents it from being taken up by the test organism. We also found that zopfiellin acted by affecting a basic physiological process called gluconeogenesis.

Technical Abstract: Zopfiellin, a novel cyclooctanoid natural product isolated from Zopfiella curvata No.37-3, was evaluated for antifungal activity, and its mechanism of action was investigated. Fungal growth inhibition caused by zopfiellin was mediated by the pH of the growth medium. Maximum inhibitory activity was obtained between pH 5 and 5.5. Intramolecular ring closure of zopfiellin from a tetracarboxylate to an anhydride form occurring at pH below 6 is apparently required for uptake by the fungus. Biological activity of zopfiellin could be reversed by exogenous addition of oxaloacetate. The in vitro activity of zopfiellin is associated with a stimulation of phosphoenolpyruvate carboxykinase activity, a regulatory enzyme in the gluconeogenesis pathway catalyzing the conversion of oxaloacetate to phosphoenolpyruvate. The mechanism of antifungal activity of zopfiellin appears to destabilize normal physiological processes by preventing early onset of gluconeogenesis.

Last Modified: 11/22/2014