FUM15_GIBM7
ID FUM15_GIBM7 Reviewed; 596 AA.
AC W7LC91; Q8J2Q5;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Cytochrome P450 monooxygenase FUM15 {ECO:0000303|PubMed:12620260};
DE EC=1.-.-.- {ECO:0000305|PubMed:12620260};
DE AltName: Full=Fumonisin biosynthesis cluster protein 15 {ECO:0000303|PubMed:12620260};
GN Name=FUM15 {ECO:0000303|PubMed:12620260}; ORFNames=FVEG_14636;
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], AND PATHWAY.
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 [2]
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 [3]
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 [4]
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 [5]
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 [6]
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 [7]
RP FUNCTION.
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 [8]
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 [9]
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 [10]
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 [11]
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: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of fumonisins B1 (FB1), B2 (FB2), B3 (FB3),
CC and B4 (FB4), which are carcinogenic mycotoxins (PubMed:12620260). On
CC the basis of the chemical structures of fumonisins and precursor
CC feeding studies, fumonisin biosynthesis is predicted to include at
CC least five groups of biochemical reactions: synthesis of a linear
CC polyketide with a single terminal carbonyl function and methyl groups
CC at C-10 and C-14; condensation of the polyketide with alanine;
CC reduction of the polyketide carbonyl to a hydroxyl; hydroxylation of 2-
CC 4 polyketide carbons; and esterification of six-carbon tricarboxylic
CC acids to two of the hydroxyls (PubMed:12620260). The biosynthesis
CC starts with the polyketide synthase FUM1-catalyzed carbon chain
CC assembly from one molecule of acetyl CoA, eight molecules of malonyl
CC CoA, and two molecules of methionine (PubMed:10413619). The C-18
CC polyketide chain is released from the enzyme by a nucleophilic attack
CC of a carbanion, which is derived from R-carbon of alanine by
CC decarboxylation, on the carbonyl carbon of polyketide acyl chain
CC (PubMed:15137825, PubMed:12720383). This step is catalyzed by a
CC pyridoxal 5'-phosphate-dependent aminoacyl transferase FUM8
CC (PubMed:15137825, PubMed:12720383). The resultant 3-keto intermediate
CC 2-amino-3-oxo-12,16-dimethylicosane is then stereospecifically reduced
CC to the 3-hydroxyl product 2-amino-3-hydroxy-12,16-dimethylicosane by
CC reductase FUM13 (PubMed:12720383, PubMed:15137825). Subsequent
CC oxidations at C-5, C-10, C-14 and C-15 followed by tricarballylic
CC esterification of the hydroxyl groups on C-14 and C-15 furnish the
CC biosynthesis of fumonisins (PubMed:15066782, PubMed:15137825,
CC PubMed:16489749). The C-10 hydroxylation is performed by the cytochrome
CC P450 monooxygenase FUM2 and occurs early in the biosynthesis
CC (PubMed:16536629). The C-5 hydroxylation is performed by the
CC dioxygenase FUM3 and occurs late in the biosynthesis (PubMed:20237561,
CC PubMed:15066782, PubMed:15137825, PubMed:16536629). Cytochrome P450
CC monooxygenases FUM6 and FUM15 may be responsible for the two remaining
CC hydroxylations at positions C-14 and C-15 (PubMed:12620260). The FUM11
CC tricarboxylate transporter makes a tricarboxylic acid precursor
CC available for fumonisin biosynthesis via its export from the
CC mitochondria (PubMed:12620260). If the precursor is citrate, the FUM7
CC dehydrogenase could remove the C-3 hydroxyl of citrate to form
CC tricarballylic acid either before or after the CoA activation by the
CC FUM10 acyl-CoA synthetase and FUM14 catalyzed esterification of CoA-
CC activated tricarballylic acid to the C-14 and C-15 hydroxyls of the
CC fumonisin backbone (PubMed:16489749, PubMed:17147424). Alternatively,
CC if the precursor is cis-aconitate, FUM7 may function to reduce the
CC double bond (PubMed:17147424). In this alternate proposal, feeding
CC studies with tetradehydro-fumonisin B1 suggests that FUM7 cannot
CC function on the tricarballylic ester and must therefore act before the
CC FUM14-mediated esterification (PubMed:17147424).
CC {ECO:0000269|PubMed:10413619, ECO:0000269|PubMed:12620260,
CC ECO:0000269|PubMed:12720383, ECO:0000269|PubMed:14602658,
CC ECO:0000269|PubMed:15066782, ECO:0000269|PubMed:15137825,
CC ECO:0000269|PubMed:15969533, ECO:0000269|PubMed:16489749,
CC ECO:0000269|PubMed:16536629, ECO:0000269|PubMed:17147424}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:12620260}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF155773; AAN74818.2; -; Genomic_DNA.
DR EMBL; DS022242; EWG36206.1; -; Genomic_DNA.
DR RefSeq; XP_018742397.1; XM_018903583.1.
DR AlphaFoldDB; W7LC91; -.
DR SMR; W7LC91; -.
DR STRING; 334819.W7LC91; -.
DR GeneID; 30071512; -.
DR KEGG; fvr:FVEG_14636; -.
DR VEuPathDB; FungiDB:FVEG_14636; -.
DR OrthoDB; 825914at2759; -.
DR Proteomes; UP000009096; Chromosome 1.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:1900541; P:fumonisin biosynthetic process; IMP:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 3: Inferred from homology;
KW Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..596
FT /note="Cytochrome P450 monooxygenase FUM15"
FT /id="PRO_0000441143"
FT REGION 476..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 476..492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 536
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"
SQ SEQUENCE 596 AA; 67191 MW; 7A03E860B4CB1D15 CRC64;
MRGLNNIAVA LALSAIWSFG LDLGRHGTSG SSLLLALFRT LCKAYPFVVI SHFVWSAIIW
PTFFSPLRQL PNVPSDGWLS KETLRLVSEP RGVPQSDWIN SLSNRPVDLA RYRSFLGFER
LLIISPKALA EVLTTKSYDF RKPGLIVSEL KQATGMGVLL AEGSEHKSQR KALQTAFNYR
HIKNLYPVFW DVAGEFATVL EKQIPTGTPR TSDTTAVIDI VDWASRATLD IIGRAGMGQG
FDAIQNDDSR LHQAYRMIFE PSRGAIFLAL LRLIFPERLV NWLPLRRNKR MRHGIQVIRS
KCQELIRERK EKIKRQKAGV DNSGNDILTV ALLNGVFTDE QLIDQLMTFL AAGHETTATA
LTWAIYILCK QPEVQNRLRE EIRMHFPNPK GWPRSERPSS NTLQQAIDFK LPYLNVVCLE
VMRYFAPIPL TMREATCDTT ILHTFVPAGT RIILAPRVTN RDSALWGPDA NNFNPDRWLS
PKNGNREATE QSKFKIGNQK RDSTAAPEVT QEEVRGRTEA RSNYADLTFL HGPRSCIGQS
FARVEFAILL ATLIANFEFQ IEDESLLDER NISISRGATS RIVGGLKVRV RPIAVV
