Aflatoxin Biosynthesis

June 2011 135 23 3 4 1, 2 Aflatoxin Biosynthesis Kimiko Y67: 1, and Hiromitsu N6@6?>B6 2 1 National Food Research Institute, National Agricultural Research Organization (NARO), Tsukuba, Ibaraki 305 8642, Japan; 2 Faculty of Agriculture, Tottori University, Koyama, Tottori 680 8553, Japan; Corresponding author 1. 300 / / 1) 3) AF AF B 1 (AFB 1 ) AF AFB 1 P450 Q 1,P 1,M 1 AFB 1 P450 AFB 1-8,9- DNA 4) AFB 1 AFB 1-8,9- AF 250 AF AF 5), 6) 1 305 8642 2 1 12 7) AF AF AF AF AF AF 8) AF 9) 12) AF AF AF AF AF AF 2. AF A. flavus A. parasiticus Aspergillus flavus A. flavus A. parasiticus AF AF A. flavus AF 13) A. flavus

136 Vol. 52, No. 3 AF AF AF AF 14) AF AF AF AF AF AF AF AF 15 17) 3. AF AFB 1,AFB 2, AFG 1,AFG 2 AF AFM 1,AFM 2 1 AFB 1,AFB 2,AFM 1 difurocoumarocyclopentenone AFG 1,AFG 2, AFM 2 difurocoumaro-d-lactone 1 AF (AFB 1,AFG 1,AFM 1 ) 2 (AFB 2, AFG 2, AFM 2 ) AFM 1, AFM 2 14 AFB 1,AFB 2 AF 15) 17) AF AF 28 AF 37 AF AF AF AF 25 70 kb A. flavus 8 AF III 16), 17) 2 AF ORF 19) AF aflr AF 1. AF AFM 1,AFM 2 AflR AF 20), 21) 4. A. oryzae A. sojae A. flavus AF FDA GRAS (Generally Recognized As Safe) 2005 19 A. oryzae A. oryzae AF 22), 23) AF AF 24) AF 25) A. oryzae A. sojae A. flavus A. parasiticus

June 2011 137 norb cypa aflt pksa hypb1 nor-1 fas-2 fas-1 aflr aflj NI 26 NI 2 NI 5 1 1 R (R) adha esta nora ver-1 vera avna hypb2 verb avfa dmta 7 11 NI 16 16 6 NI 15 9 17 omta orda vbs cypx moxy ordb hypa nada vrda 18 19 25, (27) 8, 14 9 10 16 16 29 12 2. 3, 4 hypb1 hypb2 AF vrda R, NI, 3-1. A. flavus A. parasiticus 5. AF acetyl CoA 28 AF AF

138 Vol. 52, No. 3 3-2. DMST HOMST VB (22) (24) G-AF 2 AF 3 17) (1) (4) Acetyl CoA norsolorinic acid (NA) AF 2 fas1 fas2 26) acetyl CoA malonyl CoA C6 hexanoyl CoA Hexanoyl CoA 27), pksa (polyketide synthase) CoA hexanoyltetrahydroxyanthrone (HexAT) 28), 29) HexAT C10 norsolorinic acid (NA) hypb1 19) NA NA NA AF 10) 12) (5) NA averantin (AVN) NA NA reductase NADPH NADH averantin (AVN) 30) AVN NAD(P) NA

June 2011 139 AF NA reductase AF AF nor-1 10 31) Nor-1 AF (13R,14S)-( )-aflatoxin 1 AF AF AF AVN (1 S)-( ) NA 1 (HPLC) AVN NA (1 S)-( )-AVN (1 R)- ( )-AVN 32) NADP (1 S)-( )-AVN NA (1 R)-( )- AVN NA reductase NA AVN AVR (8) AF Emericella heterothallica AVN (1 S)-( )-AVN (1 R)-( )-AVN (6) AVN 5 -hydroxyaverantin (HAVN) AVN (AVN monooxygenase) 5 -hydroxyaverantin (HAVN) 30), 32) avna 33) (1 S)-( )-AVN (1 S, 5 S)-HAVN (1 S, 5 R)-HAVN 2:1 (1 R)-( )-AVN 32) AVN (monooxygenase) AVN 1 5 HAVN Emericella heterothallica 30) AF (7) HAVN 5 -oxoaverantin (OAVN) (1 S, 5 S)-HAVN (1 S, 5 R)-HAVN (HAVN dehydrogenase) (1 S)-5 -oxoaverantin (OAVN) 32) 5 adha 34) NAD NADP OAVN OAVN HAVN dehydrogenase 35) acetyl methionine sulfoxide 60 kda (8) OAVN averufin (AVR) (1 S)-OAVN OAVN (cyclase) (1 S, 5 S)-AVR 32) 158 kda 36) AF (1 S, 5 S)-AVR (1 S)-OAVN (1 S, 5 S)-AVR OAVN 1 S NA reductase (5) AVR 32), 36) OAVN (cyclase) VHOH cyclase (VBS) VHOH cyclase (14) 36) VHOH VB (9) AVR hydroxyversicolorone (HVN) avfa cypx AVR HVN 38), 39) AvfA CypX P450 2 cypx AF avfa AF Cai, (1 S, 5 S)-AVR NADPH hydroxyversicolorone (HVN) 37) AvfA (10) HVN versiconal hemiacetal acetate (VHA) HVN NADPH HVN (monooxygenase) versi-

140 conal hemiacetal acetate (VHA) 37) 40) moxy HVN versicolorone (VONE) moxy HVN monooxygenase 39) HVN VONE (12) Vol. 52, No. 3 AF VHA reductase vrda vrda AF 44) vrda aflr AF AF AF (11) VHA versiconal (VHOH) VHA esta VHA (esterase) versiconal (VHOH) 41) (DV) 42) DV AF AF VHA versiconol acetate (VOAc) 43) esta VHA VOAc 41) VOAc (12) Esterase VHA VHOH VOAc versiconol (VOH) esta 30 41) esterase VHOH VHA (12), (13) VHA reductase versicolorol (VONOL) HVN, VHA, VHOH NADPH VHA reductase VONE, VOAc, VOH 43), 44) VONE, VOAc, VOH feeding AF VONE, VOAc, VOH AF 43) VONE VOAc HVN VHA monooxygenase esterase HVN VHA VHOH VONE VOAc VOH VHA reductase 6 37), 43) VONE NADPH versicolorol (VONOL) (14) VHOH versicolorin B (VB) VHOH VHOH cyclase (1 R, 2 S)-versicolorin B (VB) 37), 45) AF vbs (versicolorin B synthetase) 46) VHOH cyclase AF OAVN cyclase VHOH cyclase 1 2 (8) (14) (8) OAVN AVR OAVN cyclase N VHOH VB VHOH cyclase (VBS) 36), 46) VBS vbs VHOH OAVN HAVN AF cyclase vbs 1 1 AF 2 36) AF AF AF HVN, VHA, VHOH (1 R, 2 S) (1 S, 2 R) AF HPLC VHOH cyclase VHOH (1 R, 2 S)-VB 47) VHOH VHOH (1 R, 2 S) (1 S, 2 R) versicolorin C (VC) VHOH (1 R, 2 S)- VB HPLC cyclase

June 2011 141 (1 R, 2 S)- (1 R, 2 S)-VB 47) (1 S, 2 R)-VHOH (1 R, 2 S)- VHOH (1 S, 2 R)- VHOH (1 R, 2 S)-VHOH VHOH cyclase VB (1 R, 2 S)- VB AF AF VHOH cyclase VHOH cyclase OAVN (15) VB versicolorin A (VA) (1 R, 2 S)-VB desaturase VA 48) (1 S, 2 R)- VB 47) Desaturase 48) VB AFB 2,AFG 2 tetrahhydrobisfuran versicolorin A (VA) AFB 1,AFG 1 dihydrobisfuran AF feeding VB 4 AF VA AFB 1 AFG 1 48) Desaturase verb 49) verb 1 AF (AFB 1,AFG 1 ) 2 AF (AFB 2,AFG 2 ) desaturase 2 AF 1 AF (16) VA demethylsterigmatocystin (DMST) VB dihydrodemethylsterigmatocystin (DHDMST) VA demethylsterigmatocystin (DMST) VA DMST VA DMST AF ver-1, ordb, hypx AF VA 50) 52) VA DMST 3 vera 53) VB DHDMST AF 2) (17) DMST sterigmatocystin (ST) DHDMST dihydrosterigmatocystin (DHST) DMST DHDMST 2 OH 6- OH 7-OH, S-adenosylmethionine O-methyltransferase I 6-OH ST DHST 54), 55) O- Methyltransferase I 90 kda K m 1 2 M 100 mm 55) AF O-Methyltransferase I dmta 56) (18) ST O-methylsterigmatocystin (OMST) DHST dihydro-o-methylsterigmatocystin (DHOMST) ST DHST 7-OH S-adenosylmethionine O-methyltransferase II OMST DHOMST O-Methyltransferase II DMST DHDMST 7-OH 6-OH 7-OH 55) O-Methyltransferase II omta 57) (19) OMST 11-hydroxy-O-methylsterigmatocystin (HOMST) DHOMST dihydro- 11-hydroxy-O-methylsterigmatocystin (DHHOMST) orda OrdA P450 OMST AFB 1 58) 60) orda OMST DHOMST 4 AF OrdA G-AF OMST AF OrdA OMST AFB 1 11 -hydroxy-o-methylsterigmatocystin (HOMST) 61), 62) OMST HOMST, OMST dihydro DHOMST DHHOMST OrdA

142 (20) (24), (25) HOMST AFB 1 DHHOMST AFB 2 HOMST AFB 1 DHHOMST AFB 2 OrdA 61), 62) aryl ring cleavage, demethylation, dehydration, decarboxylation OrdA (20) (24), (26) (29) HOMST AFG 1 DHHOMST AFG 2 HOMST DHHOMST AFB 1,AFB 2 AFG 1,AFG 2 HOMST feeding AFB 1 AFG 1 DHH- OMST AFB 2 AFG 2 62) HOMST AFG 1 AFB 1 cypa G-AF B-AF CypA 63) HOMST AFG 1 HOMST AFG 1 3 2 1 62) OrdA CypA (29) NADA AFG 1 DHNADA AFG 2 nada G-AF NADA 64) NADA 360 AFG 1 NadA NAD(P)H NADA AFG 1 NADA dihydro DHNADA AFG 2 NadA G-AF HOMST AFG 1 NadA 64) HOMST AFG 1 6. AF NADPH acetyl CoA 1 AF 10 NADPH NAD 1 S-adenosylmethionine (SAM) 2 Vol. 52, No. 3 malonyl CoA SAM NADPH AF AF AF YES 20 5 AF NADPH NADPH AF AF AF AF AF AF AF nor-1 31) esta 41) AF vrda AF 44) vrda AflR AF AF vrda VONE AF VOROL 37) AF AF AF AF AF AF AF NA AVN OMT-I 1 cyclase 2 AF

June 2011 143 AF 7. A. parasiticus AFB 1,AFB 2,AFG 1,AFG 2 A. flavus B-AF (AFB 1,AFB 2 ) AF A. flavus AF 1 1.5 kb G-AF cypa cypa Aspergillus flavus G-AF 63) B-AF G-AF HOMST AFB 1 OrdA HOMST AFG 1 OrdA 2 G-AF AF 4 AF AFM 1 AFM 2 AF M-AF AF M-AF 8. AF AF A. oryzae A. sojae AF 23), 24), 65) A. parasiticus A. flavus A. nomius, A. pseudotamarii, A. bombycis, A. ochraceoroseus, A. australis AF AF 66) A. nidulans A. versicolor 20 AF (ST) A. nidulans ST ST AF ST ST 67), 68) ST AF Mycosphaerella pini, A. fumigatus, Coccidioides immitis AF 19) A. versicolor E. hetherothallica AF AVR HAVN AF 3), 69), 70) AF 71) AF AF AF AF 9. AF AF AF AF ST OMST DHOMST AFG 1 NADA 64) AF AF 72), 73) AF feeding M AF aflt 74) 10. AF ph AF AF aflr AflR binuclear zinc cluster (Zn(II)2Cys6) DNA AF 53) aflr aflj 75) aflr camp Ca G 76) A. nidulans VeA LaeA A. flavus A. parasiticus AF

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