ID   CLM2_GIBZE              Reviewed;         529 AA.
AC   A0A098D1J7; A0A0E0RKQ1;
DT   12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT   07-JAN-2015, sequence version 1.
DT   03-AUG-2022, entry version 33.
DE   RecName: Full=Cytochrome P450 monooxygenase CLM2 {ECO:0000303|PubMed:26673640};
DE            EC=1.-.-.- {ECO:0000305|PubMed:26673640};
DE   AltName: Full=Culmorin biosynthesis protein 2 {ECO:0000303|PubMed:26673640};
GN   Name=CLM2 {ECO:0000303|PubMed:26673640}; ORFNames=FGRAMPH1_01T00053;
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   FUNCTION.
RX   PubMed=19880637; DOI=10.1128/aem.02017-09;
RA   McCormick S.P., Alexander N.J., Harris L.J.;
RT   "CLM1 of Fusarium graminearum encodes a longiborneol synthase required for
RT   culmorin production.";
RL   Appl. Environ. Microbiol. 76:136-141(2010).
RN   [5]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=26673640; DOI=10.1021/acs.jnatprod.5b00676;
RA   Bahadoor A., Schneiderman D., Gemmill L., Bosnich W., Blackwell B.,
RA   Melanson J.E., McRae G., Harris L.J.;
RT   "Hydroxylation of Longiborneol by a Clm2-Encoded CYP450 Monooxygenase to
RT   Produce Culmorin in Fusarium graminearum.";
RL   J. Nat. Prod. 79:81-88(2016).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase involved in the biosynthesis of
CC       culmorin, a tricyclic sesquiterpene diol reported to have antifungal
CC       activity and some phytotoxicity to wheat coleoptile tissue,
CC       contributing to Fusarium head blight disease (PubMed:19880637). The
CC       terpene cyclase CLM1 is responsible for the cyclization of farnesyl
CC       diphosphate into the intermediate longiborneol (PubMed:19880637).
CC       Longiborneol is then hydroxylated in a regio- and endo-stereoselective
CC       manner at position C-11 by the cytochrome P450 monooxygenase CLM2 to
CC       produce culmorin (PubMed:26673640). Additional non-specific oxygenases
CC       are also able to hydroxylate longiborneol at other sites than C-11
CC       leading to 3-hydroxylongiborneol, 5-hydroxylongiborneol, 12-
CC       hydroxylongiborneol and 15-hydroxylongiborneol (PubMed:26673640).
CC       Moreover, another oxygenase capable of installing a C-11 exo-hydroxy
CC       group in longiborneol can also yield 11-epi-acetylculmorin
CC       (PubMed:26673640). The production of these longiborneol derivatives is
CC       dwarfed by the high abundance of culmorin, suggesting that CLM2
CC       displays superior enzymatic activity to the unidentified, possibly
CC       promiscuous, additional oxygenases (PubMed:26673640).
CC       {ECO:0000269|PubMed:19880637, ECO:0000269|PubMed:26673640}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:26673640}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Leads to complete loss of culmorin production
CC       (PubMed:26673640). Accumulates 3-hydroxylongiborneol, 5-
CC       hydroxylongiborneol, 12-hydroxylongiborneol and 15-hydroxylongiborneol,
CC       suggesting that non-specific oxygenases are still able to hydroxylate
CC       longiborneol at other sites than C-11 (PubMed:26673640). Accumulates
CC       also 11-epi-acetylculmorin, pointing to the existence of an oxygenase
CC       capable of installing a C-11 exo-hydroxy group in longiborneol, whose
CC       activity is not apparent until CLM2 is disrupted (PubMed:26673640).
CC       Does not affect the trichothecene biosynthetic pathway since 15-
CC       acetyldeoxynivalenol (15ADON) is still produced (PubMed:26673640).
CC       {ECO:0000269|PubMed:26673640}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; HG970332; CEF71826.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A098D1J7; -.
DR   SMR; A0A098D1J7; -.
DR   STRING; 229533.A0A098D1J7; -.
DR   VEuPathDB; FungiDB:FGRAMPH1_01G00053; -.
DR   eggNOG; KOG0156; Eukaryota.
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   3: Inferred from homology;
KW   Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW   Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix;
KW   Virulence.
FT   CHAIN           1..529
FT                   /note="Cytochrome P450 monooxygenase CLM2"
FT                   /id="PRO_0000444958"
FT   TRANSMEM        2..19
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         438
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        244
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        281
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   529 AA;  59994 MW;  62754795D5F4B719 CRC64;
     MLLIIVVLVG TLIYFLSFHN KKRHGLPPGP KPLPIIGNIK DMPPKGVAAF RHWLKHKDTY
     GPVSSVSVLG QPLILIHDRE AAHYLFDKSS GKSSGRPSAN FGGRLCGFDQ ILSLQQYGDT
     FKRHRKLVHR QMGTRAGAAK FRQIQDVESH RFLLRSLDNP GNLMEHIRKE AGGVILKATY
     GYSIEPHKPD PLVHLVEFMV EGISIVVVPM KFVVDFLPWL EYIPECLPGM SFKARARRWR
     TILNNTIEAP YQFVRQQMAK GIQFESYVSS LLTQEKLKGG NDTLDETYEA DIKRTAAIMY
     AGGADTTVST IQSFVLAMMV YPEVLKKAQA EIDNVIGPDR LPGFEDRENL PYINSMVKES
     LRWMPAVPMG AAHKADDDIY YGDLCIPKGS FLLPNVWWFL HNPETYQDPE RYDPDRYLEP
     RNEPDPDSNC WGYGRRICPG RLLADESIFI VIARVVAAFD IEKDVDEQGN TIEPKVEFTT
     EGALSRPVDY PYRIKPRNAK CVDLIRAVEK EHPWDKGDAS LLQQDMVVL