ID   RDC4_METCM              Reviewed;         492 AA.
AC   B3FWT9;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2008, sequence version 1.
DT   03-AUG-2022, entry version 36.
DE   RecName: Full=Cytochrome P450 monooxygenase rdc4 {ECO:0000303|PubMed:18567690};
DE            EC=1.-.-.- {ECO:0000305|PubMed:18567690};
DE   AltName: Full=Hypothemycin biosynthesis cluster protein rdc4 {ECO:0000303|PubMed:18567690};
GN   Name=rdc4 {ECO:0000303|PubMed:18567690};
OS   Metacordyceps chlamydosporia (Nematophagous fungus) (Pochonia
OS   chlamydosporia).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Clavicipitaceae; Pochonia.
OX   NCBI_TaxID=280754;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC   STRAIN=ATCC 16683;
RX   PubMed=18567690; DOI=10.1128/aem.00478-08;
RA   Reeves C.D., Hu Z., Reid R., Kealey J.T.;
RT   "Genes for the biosynthesis of the fungal polyketides hypothemycin from
RT   Hypomyces subiculosus and radicicol from Pochonia chlamydosporia.";
RL   Appl. Environ. Microbiol. 74:5121-5129(2008).
RN   [2]
RP   REVIEW ON BIOTECHNOLOGY.
RX   PubMed=19860733; DOI=10.2174/156802609789895665;
RA   Winssinger N., Fontaine J.G., Barluenga S.;
RT   "Hsp90 inhibition with resorcyclic acid lactones (RALs).";
RL   Curr. Top. Med. Chem. 9:1419-1435(2009).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of radicicol, a resorcylic acid lactone (RAL)
CC       that irreversibly inhibits the HSP90 molecular chaperone, an important
CC       target for cancer chemotherapy (PubMed:18567690). The cluster encodes
CC       only two apparent post-PKS enzymes, a cytochrome P450 monooxygenase
CC       (rdc4) and a non-heme halogenase (rdc2) that could introduce the
CC       epoxide and the chlorine, respectively (PubMed:18567690). If this
CC       cluster includes all the genes required for radicicol biosynthesis, the
CC       remaining structural features of radicicol are presumably generated by
CC       the PKSs rdc1 and rdc5 (PubMed:18567690). The C-2' ketone could arise
CC       if the R-PKS rdc5 and NR-PKS rdc1 each carry out four iterations, in
CC       contrast to the five iteration-three iteration split for the
CC       hypothemycin PKSs (PubMed:18567690). The origin of the cis 5',6' double
CC       bond is not known (PubMed:18567690). The radicicol R-PKS rdc5 ER domain
CC       may catalyze either double bond isomerization or reduction in the third
CC       iteration (PubMed:18567690). {ECO:0000269|PubMed:18567690}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:18567690}.
CC   -!- BIOTECHNOLOGY: Radicicol is an important pharmacophore as an inhibitor
CC       of heat shock protein 90 (Hsp90), an ATP-dependent chaperone involved
CC       in the post-translational maturation and stabilization of over one
CC       hundred proteins, and which activity has been implicated in diverse
CC       pathologies ranging from oncology to neurodegenerative and infectious
CC       diseases (PubMed:19860733).
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; EU520419; ACD39773.1; -; Genomic_DNA.
DR   AlphaFoldDB; B3FWT9; -.
DR   SMR; B3FWT9; -.
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   1: Evidence at protein level;
KW   Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase.
FT   CHAIN           1..492
FT                   /note="Cytochrome P450 monooxygenase rdc4"
FT                   /id="PRO_0000437594"
FT   BINDING         435
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   492 AA;  55954 MW;  9BEC5D8595594E87 CRC64;
     MNVSPQLLGY VVYTAIYNVY FHPLANFPGP KYLAASRIPL AFKRLTGEEV AMTYKLHIKY
     GPYVRVSPDE LSTISTAATK DVYGHNTRAG GVPKDFKAYY MKNQRKDGTE GLLTAGDEEH
     YRQRKVFAPA FSDRAIREQE PLLKKYTDLL VAKSYEKCQT AGKVDMVMFF NFATFDFIAD
     CVFGDSLHHL ESMEYHPFLA NITATVRFSA MRRVLRSFPI LQAIFEAFMP KSMIKKRLEH
     VKFCDERVMN RLANDNPSHP DFWTLVEHAE AKGNGLTKGE MRQNGFLLLT AATETTSSLM
     SAITYLLCKN PEKMKKLQAE VRGAFKSTDE MNTITLPKLQ YLQMAIEEGL RVYPPVPGGL
     PRRVVQPGTT LDGSASNMHI QSVVFYSQYA SYHSPSHFAR PHEFIPERWS QNPPAEFAND
     RLEAVQAFSA GPRDCIGKNL AYHEARMLLA KFVFTYDIEL CKESSDWIKQ KVYIVGAKSP
     LWVKLVKHER AD