FUM6_GIBM7
ID FUM6_GIBM7 Reviewed; 1115 AA.
AC Q9HGE0; W7LC82;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Bifunctional cytochrome P450/NADPH--P450 reductase {ECO:0000303|PubMed:11728154};
DE AltName: Full=Fumonisin biosynthesis cluster protein 6 {ECO:0000303|PubMed:11728154};
DE Includes:
DE RecName: Full=Cytochrome P450 monooxygenase {ECO:0000250|UniProtKB:Q9Y8G7};
DE EC=1.14.14.1 {ECO:0000250|UniProtKB:Q9Y8G7};
DE Includes:
DE RecName: Full=NADPH--cytochrome P450 reductase {ECO:0000250|UniProtKB:Q9Y8G7};
DE EC=1.6.2.4 {ECO:0000250|UniProtKB:Q9Y8G7};
GN Name=FUM6 {ECO:0000303|PubMed:11728154}; ORFNames=FVEG_00317;
OS Gibberella moniliformis (strain M3125 / FGSC 7600) (Maize ear and stalk rot
OS fungus) (Fusarium verticillioides).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium fujikuroi species complex.
OX NCBI_TaxID=334819;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=11728154; DOI=10.1006/fgbi.2001.1299;
RA Seo J.A., Proctor R.H., Plattner R.D.;
RT "Characterization of four clustered and coregulated genes associated with
RT fumonisin biosynthesis in Fusarium verticillioides.";
RL Fungal Genet. Biol. 34:155-165(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=12620260; DOI=10.1016/s1087-1845(02)00525-x;
RA Proctor R.H., Brown D.W., Plattner R.D., Desjardins A.E.;
RT "Co-expression of 15 contiguous genes delineates a fumonisin biosynthetic
RT gene cluster in Gibberella moniliformis.";
RL Fungal Genet. Biol. 38:237-249(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=20237561; DOI=10.1038/nature08850;
RA Ma L.-J., van der Does H.C., Borkovich K.A., Coleman J.J., Daboussi M.-J.,
RA Di Pietro A., Dufresne M., Freitag M., Grabherr M., Henrissat B.,
RA Houterman P.M., Kang S., Shim W.-B., Woloshuk C., Xie X., Xu J.-R.,
RA Antoniw J., Baker S.E., Bluhm B.H., Breakspear A., Brown D.W.,
RA Butchko R.A.E., Chapman S., Coulson R., Coutinho P.M., Danchin E.G.J.,
RA Diener A., Gale L.R., Gardiner D.M., Goff S., Hammond-Kosack K.E.,
RA Hilburn K., Hua-Van A., Jonkers W., Kazan K., Kodira C.D., Koehrsen M.,
RA Kumar L., Lee Y.-H., Li L., Manners J.M., Miranda-Saavedra D.,
RA Mukherjee M., Park G., Park J., Park S.-Y., Proctor R.H., Regev A.,
RA Ruiz-Roldan M.C., Sain D., Sakthikumar S., Sykes S., Schwartz D.C.,
RA Turgeon B.G., Wapinski I., Yoder O., Young S., Zeng Q., Zhou S.,
RA Galagan J., Cuomo C.A., Kistler H.C., Rep M.;
RT "Comparative genomics reveals mobile pathogenicity chromosomes in
RT Fusarium.";
RL Nature 464:367-373(2010).
RN [4]
RP FUNCTION.
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=10413619; DOI=10.1006/fgbi.1999.1141;
RA Proctor R.H., Desjardins A.E., Plattner R.D., Hohn T.M.;
RT "A polyketide synthase gene required for biosynthesis of fumonisin
RT mycotoxins in Gibberella fujikuroi mating population A.";
RL Fungal Genet. Biol. 27:100-112(1999).
RN [5]
RP FUNCTION.
RX PubMed=14602658; DOI=10.1128/aem.69.11.6935-6937.2003;
RA Butchko R.A., Plattner R.D., Proctor R.H.;
RT "FUM9 is required for C-5 hydroxylation of fumonisins and complements the
RT meitotically defined Fum3 locus in Gibberella moniliformis.";
RL Appl. Environ. Microbiol. 69:6935-6937(2003).
RN [6]
RP FUNCTION.
RX PubMed=12720383; DOI=10.1021/jf0262007;
RA Butchko R.A., Plattner R.D., Proctor R.H.;
RT "FUM13 encodes a short chain dehydrogenase/reductase required for C-3
RT carbonyl reduction during fumonisin biosynthesis in Gibberella
RT moniliformis.";
RL J. Agric. Food Chem. 51:3000-3006(2003).
RN [7]
RP FUNCTION.
RX PubMed=15066782; DOI=10.1128/aem.70.4.1931-1934.2004;
RA Ding Y., Bojja R.S., Du L.;
RT "Fum3p, a 2-ketoglutarate-dependent dioxygenase required for C-5
RT hydroxylation of fumonisins in Fusarium verticillioides.";
RL Appl. Environ. Microbiol. 70:1931-1934(2004).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=15137825; DOI=10.1021/jf035429z;
RA Bojja R.S., Cerny R.L., Proctor R.H., Du L.;
RT "Determining the biosynthetic sequence in the early steps of the fumonisin
RT pathway by use of three gene-disruption mutants of Fusarium
RT verticillioides.";
RL J. Agric. Food Chem. 52:2855-2860(2004).
RN [9]
RP FUNCTION.
RX PubMed=15969533; DOI=10.1021/jf050062e;
RA Yi H., Bojja R.S., Fu J., Du L.;
RT "Direct evidence for the function of FUM13 in 3-ketoreduction of mycotoxin
RT fumonisins in Fusarium verticillioides.";
RL J. Agric. Food Chem. 53:5456-5460(2005).
RN [10]
RP FUNCTION.
RX PubMed=16489749; DOI=10.1021/bi052085s;
RA Zaleta-Rivera K., Xu C., Yu F., Butchko R.A., Proctor R.H.,
RA Hidalgo-Lara M.E., Raza A., Dussault P.H., Du L.;
RT "A bidomain nonribosomal peptide synthetase encoded by FUM14 catalyzes the
RT formation of tricarballylic esters in the biosynthesis of fumonisins.";
RL Biochemistry 45:2561-2569(2006).
RN [11]
RP FUNCTION.
RX PubMed=16536629; DOI=10.1021/jf0527706;
RA Proctor R.H., Plattner R.D., Desjardins A.E., Busman M., Butchko R.A.;
RT "Fumonisin production in the maize pathogen Fusarium verticillioides:
RT genetic basis of naturally occurring chemical variation.";
RL J. Agric. Food Chem. 54:2424-2430(2006).
RN [12]
RP FUNCTION.
RX PubMed=17147424; DOI=10.1021/jf0617869;
RA Butchko R.A., Plattner R.D., Proctor R.H.;
RT "Deletion analysis of FUM genes involved in tricarballylic ester formation
RT during fumonisin biosynthesis.";
RL J. Agric. Food Chem. 54:9398-9404(2006).
CC -!- FUNCTION: Bifunctional cytochrome P450/NADPH--P450 reductase; part of
CC the gene cluster that mediates the biosynthesis of fumonisins B1 (FB1),
CC B2 (FB2), B3 (FB3), and B4 (FB4), which are carcinogenic mycotoxins
CC (PubMed:11728154, PubMed:15137825). On the basis of the chemical
CC structures of fumonisins and precursor feeding studies, fumonisin
CC biosynthesis is predicted to include at least five groups of
CC biochemical reactions: synthesis of a linear polyketide with a single
CC terminal carbonyl function and methyl groups at C-10 and C-14;
CC condensation of the polyketide with alanine; reduction of the
CC polyketide carbonyl to a hydroxyl; hydroxylation of 2-4 polyketide
CC carbons; and esterification of six-carbon tricarboxylic acids to two of
CC the hydroxyls (PubMed:12620260). The biosynthesis starts with the
CC polyketide synthase FUM1-catalyzed carbon chain assembly from one
CC molecule of acetyl CoA, eight molecules of malonyl CoA, and two
CC molecules of methionine (PubMed:10413619). The C-18 polyketide chain is
CC released from the enzyme by a nucleophilic attack of a carbanion, which
CC is derived from R-carbon of alanine by decarboxylation, on the carbonyl
CC carbon of polyketide acyl chain (PubMed:15137825, PubMed:12720383).
CC This step is catalyzed by a pyridoxal 5'-phosphate-dependent aminoacyl
CC transferase FUM8 (PubMed:15137825, PubMed:12720383). The resultant 3-
CC keto intermediate 2-amino-3-oxo-12,16-dimethylicosane is then
CC stereospecifically reduced to the 3-hydroxyl product 2-amino-3-hydroxy-
CC 12,16-dimethylicosane by reductase FUM13 (PubMed:12720383,
CC PubMed:15137825). Subsequent oxidations at C-5, C-10, C-14 and C-15
CC followed by tricarballylic esterification of the hydroxyl groups on C-
CC 14 and C-15 furnish the biosynthesis of fumonisins (PubMed:15066782,
CC PubMed:15137825, PubMed:16489749). The C-10 hydroxylation is performed
CC by the cytochrome P450 monooxygenase FUM2 and occurs early in the
CC biosynthesis (PubMed:16536629). The C-5 hydroxylation is performed by
CC the dioxygenase FUM3 and occurs late in the biosynthesis
CC (PubMed:20237561, PubMed:15066782, PubMed:15137825, PubMed:16536629).
CC Cytochrome P450 monooxygenases FUM6 and FUM15 may be responsible for
CC the two remaining hydroxylations at positions C-14 and C-15
CC (PubMed:12620260). The FUM11 tricarboxylate transporter makes a
CC tricarboxylic acid precursor available for fumonisin biosynthesis via
CC its export from the mitochondria (PubMed:12620260). If the precursor is
CC citrate, the FUM7 dehydrogenase could remove the C-3 hydroxyl of
CC citrate to form tricarballylic acid either before or after the CoA
CC activation by the FUM10 acyl-CoA synthetase and FUM14 catalyzed
CC esterification of CoA-activated tricarballylic acid to the C-14 and C-
CC 15 hydroxyls of the fumonisin backbone (PubMed:16489749,
CC PubMed:17147424). Alternatively, if the precursor is cis-aconitate,
CC FUM7 may function to reduce the double bond (PubMed:17147424). In this
CC alternate proposal, feeding studies with tetradehydro-fumonisin B1
CC suggests that FUM7 cannot function on the tricarballylic ester and must
CC therefore act before the FUM14-mediated esterification
CC (PubMed:17147424). {ECO:0000269|PubMed:10413619,
CC ECO:0000269|PubMed:12620260, ECO:0000269|PubMed:12720383,
CC ECO:0000269|PubMed:14602658, ECO:0000269|PubMed:15066782,
CC ECO:0000269|PubMed:15137825, ECO:0000269|PubMed:15969533,
CC ECO:0000269|PubMed:16489749, ECO:0000269|PubMed:16536629,
CC ECO:0000269|PubMed:17147424}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC Evidence={ECO:0000250|UniProtKB:Q9Y8G7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADPH + 2 oxidized [cytochrome P450] = H(+) + NADP(+) + 2
CC reduced [cytochrome P450]; Xref=Rhea:RHEA:24040, Rhea:RHEA-
CC COMP:14627, Rhea:RHEA-COMP:14628, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:55376, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:60344; EC=1.6.2.4;
CC Evidence={ECO:0000250|UniProtKB:Q9Y8G7};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q9Y8G7};
CC Note=Binds 1 FAD. {ECO:0000250|UniProtKB:Q9Y8G7};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q9Y8G7};
CC Note=Binds 1 FMN. {ECO:0000250|UniProtKB:Q9Y8G7};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:11728154,
CC ECO:0000269|PubMed:15137825}.
CC -!- INDUCTION: Expression correlates with fuminisins production
CC (PubMed:11728154). {ECO:0000269|PubMed:11728154}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of fumonisins
CC (PubMed:11728154, PubMed:15137825). {ECO:0000269|PubMed:11728154,
CC ECO:0000269|PubMed:15137825}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the cytochrome P450
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EWG36196.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF155773; AAG27132.1; -; Genomic_DNA.
DR EMBL; DS022242; EWG36196.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_018742387.1; XM_018886755.1.
DR AlphaFoldDB; Q9HGE0; -.
DR SMR; Q9HGE0; -.
DR STRING; 117187.FVEG_00317T0; -.
DR GeneID; 30058695; -.
DR KEGG; fvr:FVEG_00317; -.
DR eggNOG; KOG0157; Eukaryota.
DR eggNOG; KOG1158; Eukaryota.
DR OMA; ASYNGEP; -.
DR OrthoDB; 174046at2759; -.
DR Proteomes; UP000009096; Chromosome 1.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0003958; F:NADPH-hemoprotein reductase activity; IEA:UniProtKB-EC.
DR GO; GO:1900541; P:fumonisin biosynthetic process; IMP:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR Gene3D; 1.20.990.10; -; 1.
DR Gene3D; 3.40.50.360; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR023206; Bifunctional_P450_P450_red.
DR InterPro; IPR003097; CysJ-like_FAD-binding.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR008254; Flavodoxin/NO_synth.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_alpha.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR Pfam; PF00667; FAD_binding_1; 1.
DR Pfam; PF00258; Flavodoxin_1; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR Pfam; PF00067; p450; 1.
DR PIRSF; PIRSF000209; Bifunctional_P450_P450R; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR SUPFAM; SSF52218; SSF52218; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
PE 2: Evidence at transcript level;
KW Coiled coil; Electron transport; FAD; Flavoprotein; FMN; Heme; Iron;
KW Metal-binding; Monooxygenase; Multifunctional enzyme; NADP; Oxidoreductase;
KW Reference proteome; Transport.
FT CHAIN 1..1115
FT /note="Bifunctional cytochrome P450/NADPH--P450 reductase"
FT /id="PRO_0000441144"
FT DOMAIN 522..664
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 703..952
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 16..494
FT /note="Cytochrome P450"
FT /evidence="ECO:0000250|UniProtKB:Q9Y8G7"
FT REGION 488..515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 495..1115
FT /note="NADPH-P-450 reductase"
FT /evidence="ECO:0000250|UniProtKB:Q9Y8G7"
FT COILED 219..246
FT /evidence="ECO:0000255"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 493..507
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 422
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT BINDING 528..533
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P14779"
FT BINDING 528..532
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 576..579
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P14779"
FT BINDING 607..639
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 618
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:P14779"
FT SITE 288
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:P14779"
SQ SEQUENCE 1115 AA; 123277 MW; 5C6D2B947AE86C25 CRC64;
MSATALFTRR SVSTSNPELR PIPGPKPLPL LGNLFDFDFD NLTKSLGELG KIHGPIYSIT
FGASTEIMVT SREIAQELCD ETRFCKLPGG ALDVMKAVVG DGLFTAETSN PKWAIAHRII
TPLFGAMRIR GMFDDMKDIC EQMCLRWARF GPDEPLNVCD NMTKLTLDTI ALCTIDYRFN
SFYRENGAAH PFAEAVVDVM TESFDQSNLP DFVNNYVRFR AMAKFKRQAA ELRRQTEELI
AARRQNPVDR DDLLNAMLSA KDPKTGEGLS PESIVDNLLT FLIAGHETTS SLLSFCFYYL
LENPHVLRRV QQEVDTVVGS DTITVDHLSS MPYLEAVLRE TLRLRDPGPG FYVKPLKDEV
VAGKYAVNKD QPLFIVFDSV HRDQSTYGAD ADEFRPERML KDGFDKLPPC AWKPFGNGVR
ACVGRPFAMQ QAILAVAMVL HKFDLVKDES YTLKYHVTMT VRPVGFTMKV RLRQGQRATD
LAMGLHRGHS QEASAAASPS RASLKRLSSD VNGDDTDHKS QIAVLYASNS GSCEALAYRL
AAEATERGFG IRAVDVVNNA IDRIPVGSPV ILITASYNGE PADDAQEFVP WLKSLESGRL
NGVKFAVFGN GHRDWANTLF AVPRLIDSEL ARCGAERVSL MGVSDTCDSS DPFSDFERWI
DEKLFPELET PHGPGGVKNG DRAVPRQELQ VSLGQPPRIT MRKGYVRAIV TEARSLSSPG
VPEKRHLELL LPKDFNYKAG DHVYILPRNS PRDVVRALSY FGLGEDTLIT IRNTARKLSL
GLPLDTPITA TDLLGAYVEL GRTASLKNLW TLVDAAGHGS RAALLSLTEP ERFRAEVQDR
HVSILDLLER FPDIDLSLSC FLPMLAQIRP RAYSFSSAPD WKPGHATLTY TVVDFATPAT
QGINGSSKSK AVGDGTAVVQ RQGLASSYLS SLGPGTSLYV SLHRASPYFC LQKSTSLPVI
MVGAGTGLAP FRAFLQERRM AAEGAKQRFG PALLFFGCRG PRLDSLYSVE LEAYETIGLV
QVRRAYSRDP SAQDAQGCKY VTDRLGKCRD EVARLWMDGA QVLVCGGKKM ANDVLEVLGP
MLLEIDQKRG ETTAKTVVEW RARLDKSRYV EEVYV
