ID   CLAJ_PENCR              Reviewed;         438 AA.
AC   A0A481WPJ6;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   05-JUN-2019, sequence version 1.
DT   03-AUG-2022, entry version 8.
DE   RecName: Full=Cytochrome P450 monooxygenase claJ {ECO:0000303|PubMed:30811183};
DE            EC=1.-.-.- {ECO:0000305|PubMed:30811183};
DE   AltName: Full=Clavatol biosynthesis cluster protein J {ECO:0000303|PubMed:30811183};
GN   Name=claJ {ECO:0000303|PubMed:30811183};
OS   Penicillium crustosum (Blue mold fungus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=36656;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP   PATHWAY.
RC   STRAIN=PRB-2;
RX   PubMed=30811183; DOI=10.1021/jacs.9b00110;
RA   Fan J., Liao G., Kindinger F., Ludwig-Radtke L., Yin W.B., Li S.M.;
RT   "Peniphenone and penilactone formation in Penicillium crustosum via 1,4-
RT   Michael additions of ortho-quinone methide from hydroxyclavatol to gamma-
RT   butyrolactones from Crustosic Acid.";
RL   J. Am. Chem. Soc. 141:4225-4229(2019).
RN   [2]
RP   FUNCTION.
RX   PubMed=31860310; DOI=10.1021/acs.joc.9b02971;
RA   Liao G., Fan J., Ludwig-Radtke L., Backhaus K., Li S.M.;
RT   "Increasing Structural Diversity of Natural Products by Michael Addition
RT   with ortho-Quinone Methide as the Acceptor.";
RL   J. Org. Chem. 85:1298-1307(2020).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the cla gene cluster
CC       that produces clavatol and ortho-quinone methide (PubMed:30811183). The
CC       clavatol biosynthesis cluster cla and the terrestric acid cluster tra
CC       are both involved in the production of peniphenones and penilactones
CC       (PubMed:30811183). The non-reducing PKS claF is responsible for the
CC       formation of clavatol from successive condensations of 3 malonyl-CoA
CC       units, presumably with a simple acetyl-CoA starter unit, and 2
CC       methylation steps (PubMed:30811183). The esterase claE probably
CC       collaborates with claF by catalyzing the hydrolysis of ACP-bound acyl
CC       intermediates to free the ACP from stalled intermediates (By
CC       similarity). The clavatol oxidase claD then converts clavatol to
CC       hydroxyclavatol (PubMed:30811183). Spontaneous dehydration of
CC       hydroxyclavatol leads to the accumulation of the highly active ortho-
CC       quinone methide (PubMed:30811183, PubMed:31860310). On the other hand,
CC       the PKS-NRPS hybrid traA is involved in the formation of crustosic
CC       acid, with the help of traB and traD (PubMed:30811183). The polyketide
CC       synthase module (PKS) of traA is responsible for the synthesis of the
CC       polyketide backbone via the condensation of an acetyl-CoA starter unit
CC       with 3 malonyl-CoA units (PubMed:30811183). The downstream nonribosomal
CC       peptide synthetase (NRPS) module then amidates the carboxyl end of the
CC       polyketide with L-malic acid (PubMed:30811183). Because traA lacks a
CC       designated enoylreductase (ER) domain, the required activity is
CC       provided the enoyl reductase traG (By similarity). Crustosic acid
CC       undergoes decarboxylation and isomerization to the terrestric acid,
CC       catalyzed by the 2-oxoglutarate-dependent dioxygenase traH
CC       (PubMed:30811183). Both acids are further converted to the 2 gamma-
CC       butyrolactones (R)-5-methyltetronic acid and (S)-5-
CC       carboxylmethyltetronic acid, with involvement of the cytochrome P450
CC       monooxygenase claJ (PubMed:30811183). Spontaneous addition of the
CC       methide to these gamma-butyrolactones leads to peniphenone D and
CC       penilactone D, which undergo again stereospecific attacking by methide
CC       to give penilactones A and B (PubMed:30811183, PubMed:31860310).
CC       {ECO:0000250|UniProtKB:A0A0E0RXA7, ECO:0000250|UniProtKB:A0A161CKG1,
CC       ECO:0000269|PubMed:30811183, ECO:0000269|PubMed:31860310}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:30811183}.
CC   -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC       peniphenone D, penilactone D, penilactone A and penilactone B; but
CC       still retains the production of clavatol, hydroxyclavatol, crustosic
CC       acid and terrestric acid. {ECO:0000269|PubMed:30811183}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; MK360918; QBK15048.1; -; Genomic_DNA.
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   Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase.
FT   CHAIN           1..438
FT                   /note="Cytochrome P450 monooxygenase claJ"
FT                   /id="PRO_0000455066"
FT   BINDING         378
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   438 AA;  49573 MW;  3B695C42D6F72676 CRC64;
     MKGPIVRITP NELHIKDASF YDEIYAGSGR IRNKDERFVK TFSAPHAMVS ITDHAYHRVR
     RGLLGEFFSQ RSVIKMEPII NGAIEKLSQR LHEACQTGAV INMDAAFAAM TADVITRHAW
     GQSGNYLDHG NFNKQWKDAV AGTMASRVLF RHFPYMLHIL MAVPLPILLK LDPGVADILK
     IEGLVRRLSV ENVNRGIVEK QEGKTIFDAL NNVSVPPEQR TAKHLIDEGH ILLLAGTETT
     AKALSTCLCY LLLAENKNVL LALQSELRQA FPNVSTWPKW TEAQKLPYLT AVINECLRLS
     HGLSTRLPRT APKESLQYKQ WHIPAATPVS QTAYFVHMDP SIFPDPERFE PERWIRASKE
     GLHLERYIVS FSKGSRQCLG INMAYAEIFL ALTHIMRNFE FQLHDTSVDD VRLFRDRFFG
     AAQDGSVGVR VLVNEVKY