ID   RDC2_METCM              Reviewed;         519 AA.
AC   B3FWT7;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2008, sequence version 1.
DT   03-AUG-2022, entry version 30.
DE   RecName: Full=Non-heme halogenase rdc2 {ECO:0000303|PubMed:18567690};
DE            EC=1.14.14.- {ECO:0000305|PubMed:18567690};
DE   AltName: Full=Hypothemycin biosynthesis cluster protein rdc2 {ECO:0000303|PubMed:18567690};
DE   Flags: Precursor;
GN   Name=rdc2 {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: Non-heme halogenase; part of the gene cluster that mediates
CC       the biosynthesis of radicicol, a resorcylic acid lactone (RAL) that
CC       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=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:P95480};
CC       Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P95480};
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 flavin-dependent halogenase family.
CC       {ECO:0000305}.
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DR   EMBL; EU520419; ACD39771.1; -; Genomic_DNA.
DR   AlphaFoldDB; B3FWT7; -.
DR   SMR; B3FWT7; -.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR006905; Flavin_halogenase.
DR   Pfam; PF04820; Trp_halogenase; 2.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   1: Evidence at protein level;
KW   FAD; Flavoprotein; Monooxygenase; Oxidoreductase; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..519
FT                   /note="Non-heme halogenase rdc2"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000437614"
FT   BINDING         14..17
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P95480"
FT   BINDING         37..48
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P95480"
FT   BINDING         324..325
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /evidence="ECO:0000250|UniProtKB:P95480"
SQ   SEQUENCE   519 AA;  56551 MW;  9DC54E4549F49671 CRC64;
     MSVPKSCTIL VAGGGPAGSY AAAALAREGN DVVLLEADQH PRYHIGESML PSLRPLLRFI
     DLEDKFDAHG FQKKLGAAFK LTSKREGSHG PRGYSWNVVR SESDEILFNH ARESGAQAFQ
     GIKINAIEFE PYEEEYPNGE KVANPGKPTS AKWSSKDGSS GDIAFKYLVD ATGRIGIMST
     KYLKNRHYNE GLKNLAIWGY YKNNIPWAQG TPRENQPFFE GMRDGAGWCW TIPLHNGTVS
     VGAVMRKDLF FEKKKSLGEN ATNTQIMAEC MKLCPTIGEL LAPAELVSDI KQATDYSYSA
     TAYAGPNFRI VGDAGCFIDP FFSSGHHLAV AGALAAAVSI NASIKGDCTE YEASRWHAKK
     VDEGYTLFLL VVMAALKQIR MQENPVLSDV DEDGFDRAFQ FLRPEAVKKF TKEDVAQTID
     FAVHALNNMA ELDMDIPEHM INGDKEGENG VTNGNNGAAK TAGLASNMEK LTNDEEKVLN
     GLRILGKAAP GGTLADFEGT AIDGLMPRLE HGKLGLNKV