PTMK_PENSI
ID PTMK_PENSI Reviewed; 510 AA.
AC A0A140JWT9;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Cytochrome P450 monooxygenase ptmK {ECO:0000303|PubMed:25831977};
DE EC=1.-.-.- {ECO:0000269|PubMed:25831977};
DE AltName: Full=Penitrem biosynthesis cluster 2 protein K {ECO:0000303|PubMed:25831977};
GN Name=ptmK {ECO:0000303|PubMed:25831977};
OS Penicillium simplicissimum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=69488;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC STRAIN=AK-40;
RX PubMed=25831977; DOI=10.1002/anie.201501072;
RA Liu C., Tagami K., Minami A., Matsumoto T., Frisvad J.C., Suzuki H.,
RA Ishikawa J., Gomi K., Oikawa H.;
RT "Reconstitution of biosynthetic machinery for the synthesis of the highly
RT elaborated indole diterpene penitrem.";
RL Angew. Chem. Int. Ed. 54:5748-5752(2015).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the indole diterpenes penitrems
CC (PubMed:25831977). The geranylgeranyl diphosphate (GGPP) synthase ptmG
CC catalyzes the first step in penitrem biosynthesis via conversion of
CC farnesyl pyrophosphate and isopentyl pyrophosphate into geranylgeranyl
CC pyrophosphate (GGPP) (PubMed:25831977). Condensation of indole-3-
CC glycerol phosphate with GGPP by the prenyl transferase ptmC then forms
CC 3-geranylgeranylindole (3-GGI) (PubMed:25831977). Epoxidation by the
CC FAD-dependent monooxygenase ptmM leads to a epoxidized-GGI that is
CC substrate of the terpene cyclase ptmB for cyclization to yield
CC paspaline (PubMed:25831977). Paspaline is subsequently converted to 13-
CC desoxypaxilline by the cytochrome P450 monooxygenase ptmP, the latter
CC being then converted to paxilline by the cytochrome P450 monooxygenase
CC ptmQ (PubMed:25831977). Paxilline is converted to beta-paxitriol via C-
CC 10 ketoreduction by the short-chain dehydrogenase ptmH which can be
CC monoprenylated at the C-20 by the indole diterpene prenyltransferase
CC ptmD (PubMed:25831977). A two-step elimination (acetylation and
CC elimination) process performed by the O-acetyltransferase ptmV and ptmI
CC leads to the production of the prenylated form of penijanthine
CC (PubMed:25831977). The FAD-linked oxidoreductase ptmO then converts the
CC prenylated form of penijanthine into PC-M5 which is in turn transformed
CC into PC-M4 by the aromatic dimethylallyltransferase ptmE
CC (PubMed:25831977). Five sequential oxidative transformations performed
CC by the cytochrome P450 monooxygenases ptmK, ptmU, ptmL, ptmN and ptmJ
CC yield the various penitrem compounds. PtmK, ptmU and ptmM are involved
CC in the formation of the key bicyclic ring of penitrem C via the
CC formation of the intermediates secopenitrem D and penitrem D. PtmL
CC catalyzes the epoxidation of penitrem D and C to yield penitrem B and
CC F, respectively. PtmJ catalyzes the last benzylic hydroxylation to
CC convert penitrem B to prenitrem E and penitrem F to penitrem A
CC (PubMed:25831977). {ECO:0000269|PubMed:25831977}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25831977}.
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; LC027937; BAU61566.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A140JWT9; -.
DR SMR; A0A140JWT9; -.
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; 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.
PE 3: Inferred from homology;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..510
FT /note="Cytochrome P450 monooxygenase ptmK"
FT /id="PRO_0000446579"
FT TRANSMEM 2..22
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 456
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 313
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 443
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 510 AA; 57362 MW; EC0B98B10DFB2CAE CRC64;
MIIVTFFWVG IVLSAIWTFY KVVLYPYRVS PLRTLPQSQR GHWLWNHAFS EFLQPIGQLH
AELLLQIPND GMICLRGLFG APKIFLTSPK SLADVLVHRA DDFEKLPGER KILRAVVGDG
LVTAEGDVHY QQKRKLLAGF TPPKIRALYP VFWKEATALT QQIRRTLTHD GSGIYTGTTD
MVYWAPRVSM DMIGAAGFGQ SFHSLRDADS EIIHCYEKAF AIGAGHLLCV FADTLLPRII
LQWLPWPRWR QFRQNIDSIR DFCHQWVTDA KATTALGDGI PNNLLANMIH TGEYTFQELI
EQVRTFLAAG HENTSSVVMW VMLALASDSQ LQSRLRQELQ ANLPEVELDE VDLAILEQLP
LLNAVVSEAI RLFPPLPIGN RIAIRDTTVM NHPIPKGTPF LIVPRAINRS SELWGPDADR
FNADRWINPD TGRFNNHGGA SSNYSFLSFF HGPHNCIGQN FARAELRTVV AAVIRSFDMV
LDNPAADVSP VGWFTPRPAD GVKVKLRSLV
