FSL4_GIBZE
ID FSL4_GIBZE Reviewed; 557 AA.
AC I1S163;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Cytochrome P450 monooxygenase FSL4 {ECO:0000303|PubMed:22252016};
DE EC=1.-.-.- {ECO:0000305|PubMed:27983606};
DE AltName: Full=Fusarielin biosynthesis cluster protein 4 {ECO:0000303|PubMed:22252016};
GN Name=FSL4 {ECO:0000303|PubMed:22252016};
GN ORFNames=FG10461, FGRAMPH1_01T08159;
OS Gibberella zeae (strain ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084
OS / PH-1) (Wheat head blight fungus) (Fusarium graminearum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=229533;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=17823352; DOI=10.1126/science.1143708;
RA Cuomo C.A., Gueldener U., Xu J.-R., Trail F., Turgeon B.G., Di Pietro A.,
RA Walton J.D., Ma L.-J., Baker S.E., Rep M., Adam G., Antoniw J., Baldwin T.,
RA Calvo S.E., Chang Y.-L., DeCaprio D., Gale L.R., Gnerre S., Goswami R.S.,
RA Hammond-Kosack K., Harris L.J., Hilburn K., Kennell J.C., Kroken S.,
RA Magnuson J.K., Mannhaupt G., Mauceli E.W., Mewes H.-W., Mitterbauer R.,
RA Muehlbauer G., Muensterkoetter M., Nelson D., O'Donnell K., Ouellet T.,
RA Qi W., Quesneville H., Roncero M.I.G., Seong K.-Y., Tetko I.V., Urban M.,
RA Waalwijk C., Ward T.J., Yao J., Birren B.W., Kistler H.C.;
RT "The Fusarium graminearum genome reveals a link between localized
RT polymorphism and pathogen specialization.";
RL Science 317:1400-1402(2007).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=26198851; DOI=10.1186/s12864-015-1756-1;
RA King R., Urban M., Hammond-Kosack M.C.U., Hassani-Pak K.,
RA Hammond-Kosack K.E.;
RT "The completed genome sequence of the pathogenic ascomycete fungus Fusarium
RT graminearum.";
RL BMC Genomics 16:544-544(2015).
RN [4]
RP INDUCTION, AND FUNCTION.
RX PubMed=22252016; DOI=10.1111/j.1462-2920.2011.02696.x;
RA Soerensen J.L., Hansen F.T., Sondergaard T.E., Staerk D., Lee T.V.,
RA Wimmer R., Klitgaard L.G., Purup S., Giese H., Frandsen R.J.;
RT "Production of novel fusarielins by ectopic activation of the polyketide
RT synthase 9 cluster in Fusarium graminearum.";
RL Environ. Microbiol. 14:1159-1170(2012).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=27983606; DOI=10.3390/molecules21121710;
RA Droce A., Saei W., Joergensen S.H., Wimmer R., Giese H., Wollenberg R.D.,
RA Sondergaard T.E., Soerensen J.L.;
RT "Functional Analysis of the Fusarielin Biosynthetic Gene Cluster.";
RL Molecules 21:0-0(2016).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of fusarielins F, G and H, decaketide
CC compounds with 5 methylations and a decaline core that act as
CC mycoestrogens as they stimulate growth of MCF-7 breast cancer cells
CC (PubMed:22252016, PubMed:27983606). The initial compound in the pathway
CC is produced by the reducing polyketide synthase FSL1. FSL1 lacks an
CC active enoyl reductase (ER) domain and biosynthesis of fusarielins
CC relies on the trans-acting enoyl reductase FSL5, before it is released
CC through hydrolysis catalyzed by the thioesterase FSL2 (PubMed:22252016,
CC PubMed:27983606). Fusarielins F, G, and H have a C11=C12 cis double
CC bond and is fully reduced between C10 and C11 and between C12 and C13.
CC FSL3 can be involved in the formation of the C11=C12 cis double bond by
CC moving a hypothetical C10=C11 or C12=C13 trans double bond to form
CC prefusarielin (PubMed:27983606). Prefusarielin is oxygenated at C15 and
CC C16 by FSL4, resulting in fusarielin F, which subsequently is
CC epoxidized into fusarielin G by the same enzyme (PubMed:27983606). The
CC final step in the pathway is a reduction of the carboxylic acid moiety
CC to yield fusarielin H via a still undetermined mechanism
CC (PubMed:27983606). {ECO:0000269|PubMed:22252016,
CC ECO:0000269|PubMed:27983606}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:27983606}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is positively regulated by the fusarielin
CC biosynthesis cluster-specific transcription factor FSL7, probably via
CC its binding at the 5'-CGGNNNCCG-3' motif present in the promoter of all
CC the cluster genes. {ECO:0000269|PubMed:22252016}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of fusarielins F, G and
CC H, but accumulates the intermediate prefusarielin.
CC {ECO:0000269|PubMed:27983606}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; HG970332; CEF75883.1; -; Genomic_DNA.
DR RefSeq; XP_011319440.1; XM_011321138.1.
DR AlphaFoldDB; I1S163; -.
DR SMR; I1S163; -.
DR STRING; 5518.FGSG_10461P0; -.
DR GeneID; 23557366; -.
DR KEGG; fgr:FGSG_10461; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G08159; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_001570_5_11_1; -.
DR InParanoid; I1S163; -.
DR Proteomes; UP000070720; Chromosome 1.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 Gene3D; 1.10.630.10; -; 1.
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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..557
FT /note="Cytochrome P450 monooxygenase FSL4"
FT /evidence="ECO:0000255"
FT /id="PRO_0000444962"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 494
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 CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 393
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 557 AA; 62897 MW; F94F5F1367CF4366 CRC64;
MSVIGLWLVT VTATLSLFVW QLIFLLSIPK SIVVCLIAES LFFVAWFFYW TVIYPRYLTP
FRHLPTPASR SILTGNQNGL FTENSWDVAR RVSQTVPNSG LIRYYVALSN ERILVTNTRA
LSDVLTNHSH DFGKSNLAKF ALKRLTGNGL GFLEGNEHKV HRKNLMPAFT RKHVKELTPI
FWDKAMEMVK GMEAEVRCGK DTSTQGTGIV EIHDWATRAT LDIIGTAGFG YDFGTLHNPS
NEIGQQYKKM FLEPSTAFNW LELLGNYIDF RFLMTLPVKK NRDLTAGSNF MREIAKKVIR
ERRHELFQRM TSQAGNMKNT KKDIITTALA SDCFTDDQLV DHVMAFLVAG HESTATAFEW
AMYELGHRPE MQKRVRDEVR TYLPSPSAGG VKNITFESVP YLQAICNEVL RLYPFLPFAT
RVAEKDTWVA DQFVPKGTIV AYAAHISNRD SELWSGPALD AFDPERWMEP GKESSGGANS
NYAMLTFSAG PKSCIGEAWT RAELPCLVGA MVGSFEIELV EGKQADGTVY PTVDFKMGKV
LKSRDGVFVR LRRLEDW
