Spiroethers of German chamomile inhibit production of aflatoxin G₁ and trichothecene mycotoxin by inhibiting cytochrome P450 monooxygenases involved in their biosynthesis

Abstract

The essential oil of German chamomile showed specific inhibition toward aflatoxin G₁ (AFG₁) production, and (E)- and (Z)-spiroethers were isolated as the active compounds from the oil. The (E)- and (Z)-spiroethers inhibited AFG₁ production of Aspergillus parasiticus with inhibitory concentration 50% (IC₅₀) values of 2.8 and 20.8 μM, respectively, without inhibiting fungal growth. Results of an O-methylsterigmatocystin (OMST) conversion study indicated that the spiroethers specifically inhibited the OMST to AFG₁ pathway. A cytochrome P450 monooxygenase, CYPA, is known as an essential enzyme for this pathway. Because CYPA has homology with TRI4, a key enzyme catalyzing early steps in the biosynthesis of trichothecenes, the inhibitory actions of the two spiroethers against TRI4 reactions and 3-acetyldeoxynivalenol (3-ADON) production were tested. (E)- and (Z)-spiroethers inhibited the enzymatic activity of TRI4 dose-dependently and interfered with 3-ADON production by Fusarium graminearum, with IC₅₀ values of 27.1 and 103 μM, respectively. Our results suggest that the spiroethers inhibited AFG₁ and 3-ADON production by inhibiting CYPA and TRI4, respectively.

aflatoxin, CypA, deoxynivalenol, German chamomile, spiroether, Tri4