PC05_PENCR
ID PC05_PENCR Reviewed; 497 AA.
AC A0A0E3D8P5;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 24-JUN-2015, sequence version 1.
DT 03-AUG-2022, entry version 23.
DE RecName: Full=Cytochrome P450 monooxygenase PC-05 {ECO:0000303|PubMed:26213965};
DE EC=1.-.-.- {ECO:0000305|PubMed:26213965};
DE AltName: Full=Penitrem biosynthesis cluster protein PC-05 {ECO:0000303|PubMed:26213965};
GN Name=PC-05 {ECO:0000303|PubMed:26213965};
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], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC STRAIN=PN2402;
RX PubMed=26213965; DOI=10.3390/toxins7082701;
RA Nicholson M.J., Eaton C.J., Starkel C., Tapper B.A., Cox M.P., Scott B.;
RT "Molecular cloning and functional analysis of gene clusters for the
RT biosynthesis of indole-diterpenes in Penicillium crustosum and P.
RT janthinellum.";
RL Toxins 7:2701-2722(2015).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the indole diterpenes penitrems
CC (PubMed:26213965). The geranylgeranyl diphosphate (GGPP) synthase penG
CC catalyzes the first step in penitrem biosynthesis via conversion of
CC farnesyl pyrophosphate and isopentyl pyrophosphate into geranylgeranyl
CC pyrophosphate (GGPP) (Probable). Condensation of indole-3-glycerol
CC phosphate with GGPP by the prenyl transferase penC then forms 3-
CC geranylgeranylindole (3-GGI) (Probable). Epoxidation by the FAD-
CC dependent monooxygenase penM leads to a epoxidized-GGI that is
CC substrate of the terpene cyclase penB for cyclization to yield
CC paspaline (Probable). Paspaline is subsequently converted to 13-
CC desoxypaxilline by the cytochrome P450 monooxygenase penP, the latter
CC being then converted to paxilline by the cytochrome P450 monooxygenase
CC penQ (PubMed:26213965). Paxilline is converted to beta-paxitriol via C-
CC 10 ketoreduction by the short-chain dehydrogenase PC-15 which can be
CC monoprenylated at the C-20 by the indole diterpene prenyltransferase
CC penD (Probable). A two-step elimination (acetylation and elimination)
CC process performed by the O-acetyltransferase PC-16 and the
CC P.simplicissimum ptmI-ortholog not yet identified in P.crustosum, leads
CC to the production of the prenylated form of penijanthine (Probable).
CC The FAD-linked oxidoreductase ptmO then converts the prenylated form of
CC penijanthine into PC-M5 which is in turn transformed into PC-M4 by the
CC aromatic dimethylallyltransferase PC-22 (Probable). A series of
CC oxidation steps involving 4 cytochrome P450 monooxygenases (PC-21, PC-
CC 05, PC-23, PC-20) and a FAD-dependent monooxygenase (PC-14) are
CC required for the transformation of PC-M4 to penitrems A and E.
CC Synthesis of these final products is proposed to proceed via penitrems
CC D and C (PC-21, PC-05, PC-14) and penitrems B and F (PC-21, PC-05, PC-
CC 14, PC-23) (Probable). {ECO:0000269|PubMed:26213965,
CC ECO:0000305|PubMed:26213965}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:26213965}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KC963408; AGZ20187.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0E3D8P5; -.
DR SMR; A0A0E3D8P5; -.
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 GO; GO:0008152; P:metabolic process; IEA:UniProt.
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 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..497
FT /note="Cytochrome P450 monooxygenase PC-05"
FT /id="PRO_0000446584"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 434
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 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 497 AA; 56486 MW; 28A7EE5060AED28E CRC64;
MADVNTWWVG GSLLLGIWAI VVFFSPDPLA QYPFINSKRP GELFYTQSKI RFITQARSLL
KEGLSKTNNA FRLVTNNRIL LVLHSKYRNE LRDHKSLNNT KPPEDDFFGW LQGFEPFNHV
KTNPKVFAAM VRTKLTPSIG AVGIPLSEET DFVLQQQLTD SSEWHQINVK ETSLQLVARL
SARIFLGPQV CRNPAWIGIM INYTVEAFMT AERLRMWPRW LLWLVHWFLP SCKKLRSQVQ
EARGIISQVL QQREQNRKGA SLETEASDVD TVQWLEDCAK GGYYDPALLQ MGLAVVATHT
SADLLSQVIF DLCEHPELLQ PLREEIVTVI TQHGWSKNAI YNLKLLDSVL KESQRLKPMQ
INITLSDGTL IPKGTYIAMV DDHSLDPNSS YTNGDQYDGY RFIKMRDVPE RAHQTQLVSV
TSDHTGFGFG NHACPGRFFA ATELKIALCH LLLKYDLKLG DQKPQAMTYG FGLSSDPFTQ
ISVRRRQEEI SLADGKS
