ID   P4502_NEOBT             Reviewed;         541 AA.
AC   Q6F5E2;
DT   30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 1.
DT   03-AUG-2022, entry version 81.
DE   RecName: Full=Cytochrome P450 monooxygenase 2 {ECO:0000303|PubMed:14745177};
DE            EC=1.-.-.- {ECO:0000269|PubMed:21897020};
DE   AltName: Full=Aphidicolin biosynthesis protein PbP450-2 {ECO:0000305};
GN   Name=PbP450-2;
OS   Neocamarosporium betae (Beet black rot fungus) (Pleospora betae).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC   Pleosporomycetidae; Pleosporales; Pleosporineae; Pleosporaceae;
OC   Neocamarosporium.
OX   NCBI_TaxID=1979465;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND IDENTIFICATION OF GENE CLUSTER.
RC   STRAIN=PS-16;
RX   PubMed=14745177; DOI=10.1271/bbb.68.146;
RA   Toyomasu T., Nakaminami K., Toshima H., Mie T., Watanabe K., Ito H.,
RA   Matsui H., Mitsuhashi W., Sassa T., Oikawa H.;
RT   "Cloning of a gene cluster responsible for the biosynthesis of diterpene
RT   aphidicolin, a specific inhibitor of DNA polymerase alpha.";
RL   Biosci. Biotechnol. Biochem. 68:146-152(2004).
RN   [2]
RP   FUNCTION.
RX   PubMed=11457369; DOI=10.1021/ja015747j;
RA   Oikawa H., Toyomasu T., Toshima H., Ohashi S., Kawaide H., Kamiya Y.,
RA   Ohtsuka M., Shinoda S., Mitsuhashi W., Sassa T.;
RT   "Cloning and functional expression of cDNA encoding aphidicolan-16 beta-ol
RT   synthase: a key enzyme responsible for formation of an unusual diterpene
RT   skeleton in biosynthesis of aphidicolin.";
RL   J. Am. Chem. Soc. 123:5154-5155(2001).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=21897020; DOI=10.1271/bbb.110366;
RA   Fujii R., Minami A., Tsukagoshi T., Sato N., Sahara T., Ohgiya S., Gomi K.,
RA   Oikawa H.;
RT   "Total biosynthesis of diterpene aphidicolin, a specific inhibitor of DNA
RT   polymerase alpha: heterologous expression of four biosynthetic genes in
RT   Aspergillus oryzae.";
RL   Biosci. Biotechnol. Biochem. 75:1813-1817(2011).
CC   -!- FUNCTION: Geranylgeranyl pyrophosphate synthase; part of the gene
CC       cluster that mediates the biosynthesis of aphidicolin, a specific
CC       inhibitor of eukaryotic DNA synthesis and DNA polymerase alpha
CC       (PubMed:14745177, PubMed:21897020). The geranylgeranyl pyrophosphate
CC       synthase GGS is required for supplying a sufficient amount of
CC       geranylgeranyl diphosphate (GGDP), the general precursor of diterpenes
CC       (PubMed:21897020). The diterpene synthase ACS then catalyzes the
CC       conversion of geranylgeranyl diphosphate to aphidicolan-16-beta-ol via
CC       the intermediate syn-copalyldiphosphate (syn-CDP) (PubMed:11457369,
CC       PubMed:21897020). In addition to aphidicolan-16-beta-ol, the enzyme
CC       produces also low levels of amphidicol-15-ene and amphidicol-16-ene
CC       (PubMed:11457369). The cytochrome P450 monooxygenase P450-2 then
CC       catalyzes the two-step hydroxylation from aphidicolan-16-beta-ol to 3-
CC       deoxyaphidicolin via a 17,3-deoxyaphidicolin intermediate
CC       (PubMed:21897020). Finally, the cytochrome P450 monooxygenase P450-1
CC       converts 3-deoxyaphidicolin to aphidicolin (PubMed:21897020).
CC       {ECO:0000269|PubMed:11457369, ECO:0000269|PubMed:14745177,
CC       ECO:0000269|PubMed:21897020}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:21897020}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; AB079900; BAD29968.1; -; mRNA.
DR   EMBL; AB114137; BAD29974.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q6F5E2; -.
DR   SMR; Q6F5E2; -.
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; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase.
FT   CHAIN           1..541
FT                   /note="Cytochrome P450 monooxygenase 2"
FT                   /id="PRO_0000438556"
FT   BINDING         473
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   541 AA;  60668 MW;  A11569930A9E3E5D CRC64;
     MIKHSLSDCL ADPDHLIRIK SYVEANVRFL GLSLVTLLVT IQMFRALGSP LRLNKPLVGR
     RSILEPRWLV GLRFTKGGRE LLRQAYKKYK DEIFKVQCND TEICVLPHRY VEELRGLPAS
     KVSSPQALYN KGLGSYTGLE VIVESHLHFQ AIQGHLTPNL ASALGIVLDE LQDALKTVLP
     DCSDEWVPFD VHTVLSELVS RLSSRVFGGL ELARNQQWIQ LSTAYPRNAF ACTMALRMVP
     RIIRPLLAAV LPTYWRTRSN IRDAKRIVGG IITKRRADEG ATDMSAKEHP CDLLQWMMNA
     AAGTETHADD LAHRLLFISD ASVMTTSLLI SHCLYDLVAH PEALSCIREE VHNVLREGDN
     FQKTTLHKMR SLDSALKESQ RLNPPFLMTF DRVVREPLLL SDGTQIPVGT HLAMPTDAML
     QDSSLLPQGG VAPDQFDPFR YARAREDPEN AQRFQLATTE AKSLVFGHGK HACPGRFFAS
     SEAKIILSHL LLLYDFRYPE GKGRPESWLF SENVAIDPNA RLLIKKRNDA ASNLAMLAKA
     L