ID   RADP_FLOCH              Reviewed;         501 AA.
AC   C5H886;
DT   31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT   28-JUL-2009, sequence version 1.
DT   03-AUG-2022, entry version 33.
DE   RecName: Full=Cytochrome P450 monooxygenase radP {ECO:0000303|PubMed:19101477};
DE            EC=1.-.-.- {ECO:0000305|PubMed:19101477};
DE   AltName: Full=Radicicol biosynthesis cluster protein radP {ECO:0000303|PubMed:19101477};
GN   Name=radP {ECO:0000303|PubMed:19101477};
OS   Floropilus chiversii (Chaetomium chiversii).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Sordariomycetidae; Sordariales; Chaetomiaceae; Floropilus.
OX   NCBI_TaxID=2587399;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=CS-36-62;
RX   PubMed=19101477; DOI=10.1016/j.chembiol.2008.10.006;
RA   Wang S., Xu Y., Maine E.A., Wijeratne E.M., Espinosa-Artiles P.,
RA   Gunatilaka A.A., Molnar I.;
RT   "Functional characterization of the biosynthesis of radicicol, an Hsp90
RT   inhibitor resorcylic acid lactone from Chaetomium chiversii.";
RL   Chem. Biol. 15:1328-1338(2008).
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:19101477). The cluster encodes
CC       only two apparent post-PKS enzymes, a cytochrome P450 monooxygenase
CC       (radP) and a non-heme halogenase (radH) that introduce the epoxide and
CC       the chlorine, respectively (PubMed:19101477). If this cluster includes
CC       all the genes required for radicicol biosynthesis, the remaining
CC       structural features of radicicol are presumably generated by the PKSs
CC       rads1 and rads2 (PubMed:19101477). The C-2' ketone could arise if the
CC       R-PKS rads1 and NR-PKS rads2 each carry out four iterations, in
CC       contrast to the five iteration-three iteration split for the
CC       hypothemycin PKSs (PubMed:19101477). The origin of the cis 5',6' double
CC       bond is not known (By similarity). The radicicol R-PKS rads1 ER domain
CC       may catalyze either double bond isomerization or reduction in the third
CC       iteration (By similarity). {ECO:0000250|UniProtKB:B3FWT9,
CC       ECO:0000269|PubMed:19101477}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:19101477}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of radicicol and
CC       accumulates 14(15)-deepoxy-12(13)-dihydro-radicicol, also known as
CC       pochonin D (PubMed:19101477). {ECO:0000269|PubMed:19101477}.
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:19101477). {ECO:0000305|PubMed:19101477}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; EU980390; ACM42407.1; -; Genomic_DNA.
DR   AlphaFoldDB; C5H886; -.
DR   SMR; C5H886; -.
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; Transmembrane; Transmembrane helix.
FT   CHAIN           1..501
FT                   /note="Cytochrome P450 monooxygenase radP"
FT                   /id="PRO_0000443057"
FT   TRANSMEM        8..28
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         444
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        212
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   501 AA;  57108 MW;  BD4309F4D7B9D681 CRC64;
     MAEFHPTAFL LPAAVTMIAG YFLCTALYNV YFHPLAKFPG PRLYAASQIP ITIKRLLGDE
     VATFHKLHAK YGQFVRVAPG ELSTINPAAS RDVYGHRNPA KSIPKDFKAY YMKNQRRDGT
     EGLMTADDDL HRRQRKIFSP AFSDRAIREQ EPLLKKYTDL LVEKAGVASD ADGKVDMVMM
     FNFATFDFIA DCVFGDSLHL LEKMEYNPFL ANISAVVKFS AMRRAIRSFP YMDETFEKLI
     PASMKRKRME HVKFCDDLVD RRLEKAVTNH PDFWTLVLRA NEKGEGLTLG EMHQNSFLFL
     TAATETTSSL MSALTYLLCQ NPDKMKKLVD EIRGRFKSTE EMTTVSLPPL EYLQMCIEEG
     LRVYPPVPGG LPRRVTADGA SLDGRELPPD TVVYYAHYAS YHSAAHFARP DEFHPERWAS
     VPPSEFANDC RDAVIPFSAG PRDCIGKNLA YHEARLLLAK FLWTYDVELC EESKDWIKQK
     SFIVGVKRPL YVKLHRVVRE K