Spiroethers of German chamomile inhibit production of aflatoxin G and trichothecene mycotoxin by inhibiting cytochrome P450 monooxygenases involved in their biosynthesis.
The essential oil of German chamomile showed specific inhibition toward aflatoxin G(1) (AFG(1)) production, and (E)- and (Z)-spiroethers were isolated as the active compounds from the oil. The (E)- and (Z)-spiroethers inhibited AFG(1) production of Aspergillus parasiticus with inhibitory concentration 50% (IC(50)) values of 2.8 and 20.8 microM, respectively, without inhibiting fungal growth. Results of an O-methylsterigmatocystin (OMST) conversion study indicated that the spiroethers specifically inhibited the OMST to AFG(1) 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 IC(50) values of 27.1 and 103 microM, respectively. Our results suggest that the spiroethers inhibited AFG(1) and 3-ADON production by inhibiting CYPA and TRI4, respectively.
Yoshinari
Tomoya
T
Department of Applied Biological Chemistry, The University of Tokyo, Tokyo, Japan.
Yaguchi
Atsushi
A
Takahashi-Ando
Naoko
N
Kimura
Makoto
M
Takahashi
Haruo
H
Nakajima
Takashi
T
Sugita-Konishi
Yoshiko
Y
Nagasawa
Hiromichi
H
Sakuda
Shohei
S
D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000348:Aflatoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001230:Aspergillus / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004987:Ethers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005670:Fusarium / Q000201:enzymology / Q000378:metabolism; D006900:Hydroxylation; D031168:Matricaria / Q000737:chemistry*; D009822:Oils, Volatile / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013241:Sterigmatocystin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism; D014255:Trichothecenes / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000348:Aflatoxins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004987:Ethers; D009822:Oils, Volatile; D013141:Spiro Compounds; D014255:Trichothecenes; D013241:Sterigmatocystin; C039904:O-methylsterigmatocystin; C027955:aflatoxin G1; C043247:3-acetyldeoxynivalenol; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1